MutationTaster - study a chromosomal position

NEVER press reload or F5 - unless you want to start from the very beginning.
input seems to be ok - now mapping the variant to the different transcripts...
found 2 transcript(s)...
Querying Taster for transcript #1: ENST00000301732
Querying Taster for transcript #2: ENST00000382381
MT speed 0 s - this script 4.182494 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ABCA3	disease_causing_automatic	0.999999170626482	simple_aae			0	Q1591P	single base exchange	rs28936691		show file
ABCA3	disease_causing_automatic	0.999999170626482	simple_aae			0	Q1533P	single base exchange	rs28936691		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999170626482 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM040362)
known disease mutation: rs8014 (pathogenic)
protein features (might be) affected

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr16:2328017T>GN/A show variant in all transcripts IGV

HGNC symbol

ABCA3

Ensembl transcript ID

ENST00000301732

Genbank transcript ID

NM_001089

UniProt peptide

Q99758

alteration type

single base exchange

alteration region

CDS

DNA changes

c.4772A>C
cDNA.5473A>C
g.62731A>C

AA changes

Q1591P Score: 76 explain score(s)

position(s) of altered AA
if AA alteration in CDS

1591

frameshift

known variant

Reference ID: rs28936691
Allele 'G' was neither found in ExAC nor 1000G.
known disease mutation: rs8014 (pathogenic for Surfactant metabolism dysfunction, pulmonary, 3) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM040362)

known disease mutation at this position, please check HGMD for details (HGMD ID CM040362)
known disease mutation at this position, please check HGMD for details (HGMD ID CM040362)

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.032	1
	2.235	1
(flanking)	5.666	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Donor marginally increased	62732	wt: 0.9883 / mu: 0.9893 (marginal change - not scored)	wt: GGGCAGTTCAAGTGC mu: GGGCCGTTCAAGTGC	GCAG\|ttca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

1591

mutated

not conserved

1591

Ptroglodytes

all identical

ENSPTRG00000007647

1591

Mmulatta

all identical

ENSMMUG00000019242

1598

Fcatus

all identical

ENSFCAG00000007691

1591

Mmusculus

all identical

ENSMUSG00000024130

1591

Ggallus

all identical

ENSGALG00000001967

1594

Trubripes

all identical

ENSTRUG00000007310

1385

Drerio

all identical

ENSDARG00000091729

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
1381	1614	DOMAIN	ABC transporter 2.	lost

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

5115 / 5115

position (AA) of stopcodon in wt / mu AA sequence

1705 / 1705

position of stopcodon in wt / mu cDNA

5816 / 5816

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

702 / 702

chromosome

strand

-1

last intron/exon boundary

5685

theoretical NMD boundary in CDS

4933

length of CDS

5115

coding sequence (CDS) position

4772

cDNA position
(for ins/del: last normal base / first normal base)

5473

gDNA position
(for ins/del: last normal base / first normal base)

62731

chromosomal position
(for ins/del: last normal base / first normal base)

2328017

original gDNA sequence snippet

GGCCATCATGGTGCAGGGGCAGTTCAAGTGCCTGGGCAGCC

altered gDNA sequence snippet

GGCCATCATGGTGCAGGGGCCGTTCAAGTGCCTGGGCAGCC

original cDNA sequence snippet

GGCCATCATGGTGCAGGGGCAGTTCAAGTGCCTGGGCAGCC

altered cDNA sequence snippet

GGCCATCATGGTGCAGGGGCCGTTCAAGTGCCTGGGCAGCC

wildtype AA sequence

MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ
SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI
RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH
TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV
TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS
SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF
SFMVSTFFSK ANMAAAFGGF LYFFTYIPYF FVAPRYNWMT LSQKLCSCLL SNVAMAMGAQ
LIGKFEAKGM GIQWRDLLSP VNVDDDFCFG QVLGMLLLDS VLYGLVTWYM EAVFPGQFGV
PQPWYFFIMP SYWCGKPRAV AGKEEEDSDP EKALRNEYFE AEPEDLVAGI KIKHLSKVFR
VGNKDRAAVR DLNLNLYEGQ ITVLLGHNGA GKTTTLSMLT GLFPPTSGRA YISGYEISQD
MVQIRKSLGL CPQHDILFDN LTVAEHLYFY AQLKGLSRQK CPEEVKQMLH IIGLEDKWNS
RSRFLSGGMR RKLSIGIALI AGSKVLILDE PTSGMDAISR RAIWDLLQRQ KSDRTIVLTT
HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHHH
VPNATLESSA GAELSFILPR ESTHRFEGLF AKLEKKQKEL GIASFGASIT TMEEVFLRVG
KLVDSSMDIQ AIQLPALQYQ HERRASDWAV DSNLCGAMDP SDGIGALIEE ERTAVKLNTG
LALHCQQFWA MFLKKAAYSW REWKMVAAQV LVPLTCVTLA LLAINYSSEL FDDPMLRLTL
GEYGRTVVPF SVPGTSQLGQ QLSEHLKDAL QAEGQEPREV LGDLEEFLIF RASVEGGGFN
ERCLVAASFR DVGERTVVNA LFNNQAYHSP ATALAVVDNL LFKLLCGPHA SIVVSNFPQP
RSALQAAKDQ FNEGRKGFDI ALNLLFAMAF LASTFSILAV SERAVQAKHV QFVSGVHVAS
FWLSALLWDL ISFLIPSLLL LVVFKAFDVR AFTRDGHMAD TLLLLLLYGW AIIPLMYLMN
FFFLGAATAY TRLTIFNILS GIATFLMVTI MRIPAVKLEE LSKTLDHVFL VLPNHCLGMA
VSSFYENYET RRYCTSSEVA AHYCKKYNIQ YQENFYAWSA PGVGRFVASM AASGCAYLIL
LFLIETNLLQ RLRGILCALR RRRTLTELYT RMPVLPEDQD VADERTRILA PSPDSLLHTP
LIIKELSKVY EQRVPLLAVD RLSLAVQKGE CFGLLGFNGA GKTTTFKMLT GEESLTSGDA
FVGGHRISSD VGKVRQRIGY CPQFDALLDH MTGREMLVMY ARLRGIPERH IGACVENTLR
GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDE PSTGMDPVAR RLLWDTVARA
RESGKAIIIT SHSMEECEAL CTRLAIMVQG QFKCLGSPQH LKSKFGSGYS LRAKVQSEGQ
QEALEEFKAF VDLTFPGSVL EDEHQGMVHY HLPGRDLSWA KVFGILEKAK EKYGVDDYSV
SQISLEQVFL SFAHLQPPTA EEGR*

mutated AA sequence

MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ
SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI
RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH
TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV
TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS
SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF
SFMVSTFFSK ANMAAAFGGF LYFFTYIPYF FVAPRYNWMT LSQKLCSCLL SNVAMAMGAQ
LIGKFEAKGM GIQWRDLLSP VNVDDDFCFG QVLGMLLLDS VLYGLVTWYM EAVFPGQFGV
PQPWYFFIMP SYWCGKPRAV AGKEEEDSDP EKALRNEYFE AEPEDLVAGI KIKHLSKVFR
VGNKDRAAVR DLNLNLYEGQ ITVLLGHNGA GKTTTLSMLT GLFPPTSGRA YISGYEISQD
MVQIRKSLGL CPQHDILFDN LTVAEHLYFY AQLKGLSRQK CPEEVKQMLH IIGLEDKWNS
RSRFLSGGMR RKLSIGIALI AGSKVLILDE PTSGMDAISR RAIWDLLQRQ KSDRTIVLTT
HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHHH
VPNATLESSA GAELSFILPR ESTHRFEGLF AKLEKKQKEL GIASFGASIT TMEEVFLRVG
KLVDSSMDIQ AIQLPALQYQ HERRASDWAV DSNLCGAMDP SDGIGALIEE ERTAVKLNTG
LALHCQQFWA MFLKKAAYSW REWKMVAAQV LVPLTCVTLA LLAINYSSEL FDDPMLRLTL
GEYGRTVVPF SVPGTSQLGQ QLSEHLKDAL QAEGQEPREV LGDLEEFLIF RASVEGGGFN
ERCLVAASFR DVGERTVVNA LFNNQAYHSP ATALAVVDNL LFKLLCGPHA SIVVSNFPQP
RSALQAAKDQ FNEGRKGFDI ALNLLFAMAF LASTFSILAV SERAVQAKHV QFVSGVHVAS
FWLSALLWDL ISFLIPSLLL LVVFKAFDVR AFTRDGHMAD TLLLLLLYGW AIIPLMYLMN
FFFLGAATAY TRLTIFNILS GIATFLMVTI MRIPAVKLEE LSKTLDHVFL VLPNHCLGMA
VSSFYENYET RRYCTSSEVA AHYCKKYNIQ YQENFYAWSA PGVGRFVASM AASGCAYLIL
LFLIETNLLQ RLRGILCALR RRRTLTELYT RMPVLPEDQD VADERTRILA PSPDSLLHTP
LIIKELSKVY EQRVPLLAVD RLSLAVQKGE CFGLLGFNGA GKTTTFKMLT GEESLTSGDA
FVGGHRISSD VGKVRQRIGY CPQFDALLDH MTGREMLVMY ARLRGIPERH IGACVENTLR
GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDE PSTGMDPVAR RLLWDTVARA
RESGKAIIIT SHSMEECEAL CTRLAIMVQG PFKCLGSPQH LKSKFGSGYS LRAKVQSEGQ
QEALEEFKAF VDLTFPGSVL EDEHQGMVHY HLPGRDLSWA KVFGILEKAK EKYGVDDYSV
SQISLEQVFL SFAHLQPPTA EEGR*

speed

1.25 s

All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project
back to results table

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999170626482 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM040362)
known disease mutation: rs8014 (pathogenic)
protein features (might be) affected

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr16:2328017T>GN/A show variant in all transcripts IGV

HGNC symbol

ABCA3

Ensembl transcript ID

ENST00000382381

Genbank transcript ID

N/A

UniProt peptide

Q99758

alteration type

single base exchange

alteration region

CDS

DNA changes

c.4598A>C
cDNA.5310A>C
g.62731A>C

AA changes

Q1533P Score: 76 explain score(s)

position(s) of altered AA
if AA alteration in CDS

1533

frameshift

known variant

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.032	1
	2.235	1
(flanking)	5.666	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Donor marginally increased	62732	wt: 0.9883 / mu: 0.9893 (marginal change - not scored)	wt: GGGCAGTTCAAGTGC mu: GGGCCGTTCAAGTGC	GCAG\|ttca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

1533

mutated

not conserved

1533

Ptroglodytes

all identical

ENSPTRG00000007647

1591

Mmulatta

all identical

ENSMMUG00000019242

1598

Fcatus

all identical

ENSFCAG00000007691

1591

Mmusculus

all identical

ENSMUSG00000024130

1591

Ggallus

all identical

ENSGALG00000001967

1594

Trubripes

all identical

ENSTRUG00000007310

1385

Drerio

all identical

ENSDARG00000091729

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
1381	1614	DOMAIN	ABC transporter 2.	lost

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

4941 / 4941

position (AA) of stopcodon in wt / mu AA sequence

1647 / 1647

position of stopcodon in wt / mu cDNA

5653 / 5653

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

713 / 713

chromosome

strand

-1

last intron/exon boundary

5522

theoretical NMD boundary in CDS

4759

length of CDS

4941

coding sequence (CDS) position

4598

cDNA position
(for ins/del: last normal base / first normal base)

5310

gDNA position
(for ins/del: last normal base / first normal base)

62731

chromosomal position
(for ins/del: last normal base / first normal base)

2328017

original gDNA sequence snippet

GGCCATCATGGTGCAGGGGCAGTTCAAGTGCCTGGGCAGCC

altered gDNA sequence snippet

GGCCATCATGGTGCAGGGGCCGTTCAAGTGCCTGGGCAGCC

original cDNA sequence snippet

GGCCATCATGGTGCAGGGGCAGTTCAAGTGCCTGGGCAGCC

altered cDNA sequence snippet

GGCCATCATGGTGCAGGGGCCGTTCAAGTGCCTGGGCAGCC

wildtype AA sequence

MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ
SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI
RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH
TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV
TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS
SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF
SFMVSTFFSK GMGIQWRDLL SPVNVDDDFC FGQVLGMLLL DSVLYGLVTW YMEAVFPGQF
GVPQPWYFFI MPSYWCGKPR AVAGKEEEDS DPEKALRNEY FEAEPEDLVA GIKIKHLSKV
FRVGNKDRAA VRDLNLNLYE GQITVLLGHN GAGKTTTLSM LTGLFPPTSG RAYISGYEIS
QDMVQIRKSL GLCPQHDILF DNLTVAEHLY FYAQLKGLSR QKCPEEVKQM LHIIGLEDKW
NSRSRFLSGG MRRKLSIGIA LIAGSKVLIL DEPTSGMDAI SRRAIWDLLQ RQKSDRTIVL
TTHFMDEADL LGDRIAIMAK GELQCCGSSL FLKQKYGAGY HMTLVKEPHC NPEDISQLVH
HHVPNATLES SAGAELSFIL PRESTHRFEG LFAKLEKKQK ELGIASFGAS ITTMEEVFLR
VGKLVDSSMD IQAIQLPALQ YQHERRASDW AVDSNLCGAM DPSDGIGALI EEERTAVKLN
TGLALHCQQF WAMFLKKAAY SWREWKMVAA QVLVPLTCVT LALLAINYSS ELFDDPMLRL
TLGEYGRTVV PFSVPGTSQL GQQLSEHLKD ALQAEGQEPR EVLGDLEEFL IFRASVEGGG
FNERCLVAAS FRDVGERTVV NALFNNQAYH SPATALAVVD NLLFKLLCGP HASIVVSNFP
QPRSALQAAK DQFNEGRKGF DIALNLLFAM AFLASTFSIL AVSERAVQAK HVQFVSGVHV
ASFWLSALLW DLISFLIPSL LLLVVFKAFD VRAFTRDGHM ADTLLLLLLY GWAIIPLMYL
MNFFFLGAAT AYTRLTIFNI LSGIATFLMV TIMRIPAVKL EELSKTLDHV FLVLPNHCLG
MAVSSFYENY ETRRYCTSSE VAAHYCKKYN IQYQENFYAW SAPGVGRFVA SMAASGCAYL
ILLFLIETNL LQRLRGILCA LRRRRTLTEL YTRMPVLPED QDVADERTRI LAPSPDSLLH
TPLIIKELSK VYEQRVPLLA VDRLSLAVQK GECFGLLGFN GAGKTTTFKM LTGEESLTSG
DAFVGGHRIS SDVGKVRQRI GYCPQFDALL DHMTGREMLV MYARLRGIPE RHIGACVENT
LRGLLLEPHA NKLVRTYSGG NKRKLSTGIA LIGEPAVIFL DEPSTGMDPV ARRLLWDTVA
RARESGKAII ITSHSMEECE ALCTRLAIMV QGQFKCLGSP QHLKSKFGSG YSLRAKVQSE
GQQEALEEFK AFVDLTFPGS VLEDEHQGMV HYHLPGRDLS WAKVFGILEK AKEKYGVDDY
SVSQISLEQV FLSFAHLQPP TAEEGR*

mutated AA sequence

MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ
SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI
RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH
TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV
TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS
SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF
SFMVSTFFSK GMGIQWRDLL SPVNVDDDFC FGQVLGMLLL DSVLYGLVTW YMEAVFPGQF
GVPQPWYFFI MPSYWCGKPR AVAGKEEEDS DPEKALRNEY FEAEPEDLVA GIKIKHLSKV
FRVGNKDRAA VRDLNLNLYE GQITVLLGHN GAGKTTTLSM LTGLFPPTSG RAYISGYEIS
QDMVQIRKSL GLCPQHDILF DNLTVAEHLY FYAQLKGLSR QKCPEEVKQM LHIIGLEDKW
NSRSRFLSGG MRRKLSIGIA LIAGSKVLIL DEPTSGMDAI SRRAIWDLLQ RQKSDRTIVL
TTHFMDEADL LGDRIAIMAK GELQCCGSSL FLKQKYGAGY HMTLVKEPHC NPEDISQLVH
HHVPNATLES SAGAELSFIL PRESTHRFEG LFAKLEKKQK ELGIASFGAS ITTMEEVFLR
VGKLVDSSMD IQAIQLPALQ YQHERRASDW AVDSNLCGAM DPSDGIGALI EEERTAVKLN
TGLALHCQQF WAMFLKKAAY SWREWKMVAA QVLVPLTCVT LALLAINYSS ELFDDPMLRL
TLGEYGRTVV PFSVPGTSQL GQQLSEHLKD ALQAEGQEPR EVLGDLEEFL IFRASVEGGG
FNERCLVAAS FRDVGERTVV NALFNNQAYH SPATALAVVD NLLFKLLCGP HASIVVSNFP
QPRSALQAAK DQFNEGRKGF DIALNLLFAM AFLASTFSIL AVSERAVQAK HVQFVSGVHV
ASFWLSALLW DLISFLIPSL LLLVVFKAFD VRAFTRDGHM ADTLLLLLLY GWAIIPLMYL
MNFFFLGAAT AYTRLTIFNI LSGIATFLMV TIMRIPAVKL EELSKTLDHV FLVLPNHCLG
MAVSSFYENY ETRRYCTSSE VAAHYCKKYN IQYQENFYAW SAPGVGRFVA SMAASGCAYL
ILLFLIETNL LQRLRGILCA LRRRRTLTEL YTRMPVLPED QDVADERTRI LAPSPDSLLH
TPLIIKELSK VYEQRVPLLA VDRLSLAVQK GECFGLLGFN GAGKTTTFKM LTGEESLTSG
DAFVGGHRIS SDVGKVRQRI GYCPQFDALL DHMTGREMLV MYARLRGIPE RHIGACVENT
LRGLLLEPHA NKLVRTYSGG NKRKLSTGIA LIGEPAVIFL DEPSTGMDPV ARRLLWDTVA
RARESGKAII ITSHSMEECE ALCTRLAIMV QGPFKCLGSP QHLKSKFGSG YSLRAKVQSE
GQQEALEEFK AFVDLTFPGS VLEDEHQGMV HYHLPGRDLS WAKVFGILEK AKEKYGVDDY
SVSQISLEQV FLSFAHLQPP TAEEGR*

speed

0.95 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems