mutation t@sting

Prediction

disease causing

Model: simple_aae, prob: 0.999999999743618 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM093987)
known disease mutation: rs4468 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:95562509A>CN/A show variant in all transcripts IGV

HGNC symbol

DICER1

Ensembl transcript ID

ENST00000556045

Genbank transcript ID

N/A

UniProt peptide

Q9UPY3

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1442T>G
cDNA.1725T>G
g.61839T>G

AA changes

L481R Score: 102 explain score(s)

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

481

frameshift

known variant

Reference ID: rs137852976
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs4468 (pathogenic for Pleuropulmonary blastoma|DICER1-related pleuropulmonary blastoma cancer predisposition syndrome) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM093987)

known disease mutation at this position, please check HGMD for details (HGMD ID CM093987)
known disease mutation at this position, please check HGMD for details (HGMD ID CM093987)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.66	1
	4.805	1
(flanking)	5.801	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
Acc marginally increased	61842	wt: 0.8690 / mu: 0.8802 (marginal change - not scored)	wt: GGCTGCTCAGCTTTTCCTCTGTTCACTGGGGCTGAAGGTGC mu: GGCTGCTCAGCTTTTCCGCTGTTCACTGGGGCTGAAGGTGC	tctg\|TTCA
Acc gained	61838	0.49	mu: AGAGGGCTGCTCAGCTTTTCCGCTGTTCACTGGGGCTGAAG	ttcc\|GCTG

distance from splice site

348

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

481

mutated

not conserved

481

Ptroglodytes

all identical

ENSPTRG00000023484

1583

Mmulatta

all identical

ENSMMUG00000023305

1581

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000041415

1569

Ggallus

all identical

ENSGALG00000010999

1586

Trubripes

all identical

ENSTRUG00000006156

1582

Drerio

all identical

ENSDARG00000001129

1559

Dmelanogaster

all conserved

FBgn0039016

1927

Celegans

all conserved

K12H4.8

1532

Xtropicalis

all identical

ENSXETG00000023315

1563

protein features

start (aa)	end (aa)	feature	details
256	595	REGION	Required for interaction with PRKRA and TARBP2.	lost
433	602	DOMAIN	Helicase C-terminal.	lost
492	493	CONFLICT	KQ -> NT (in Ref. 1; BAA78691).	might get lost (downstream of altered splice site)
609	609	CONFLICT	D -> H (in Ref. 1; BAA78691).	might get lost (downstream of altered splice site)
630	722	DOMAIN	Dicer dsRNA-binding fold.	might get lost (downstream of altered splice site)
664	664	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
891	1042	DOMAIN	PAZ.	might get lost (downstream of altered splice site)
960	960	MUTAGEN	F->A: 2-fold decrease in activity.	might get lost (downstream of altered splice site)
971	971	MUTAGEN	Y->A: 10-fold decrease in activity; when associated with Y-972.	might get lost (downstream of altered splice site)
972	972	MUTAGEN	Y->A: 10-fold decrease in activity; when associated with Y-971.	might get lost (downstream of altered splice site)
1016	1016	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
1036	1036	MUTAGEN	E->A: 5-fold decrease in activity.	might get lost (downstream of altered splice site)
1276	1403	DOMAIN	RNase III 1.	might get lost (downstream of altered splice site)
1313	1313	MUTAGEN	E->A: No effect on activity.	might get lost (downstream of altered splice site)
1316	1316	METAL	Magnesium or manganese 1 (By similarity).	might get lost (downstream of altered splice site)
1320	1320	MUTAGEN	D->A: Decreased activity. Loss of activity; when associated with D-1709.	might get lost (downstream of altered splice site)
1340	1340	MUTAGEN	E->A: No effect on activity.	might get lost (downstream of altered splice site)
1395	1395	METAL	Magnesium or manganese 1 (By similarity).	might get lost (downstream of altered splice site)
1398	1398	METAL	Magnesium or manganese 1 (By similarity).	might get lost (downstream of altered splice site)
1444	1444	MUTAGEN	E->A: Decreased activity. Loss of activity; when associated with E-1813.	might get lost (downstream of altered splice site)
1662	1665	TURN		might get lost (downstream of altered splice site)
1666	1673	HELIX		might get lost (downstream of altered splice site)
1666	1824	DOMAIN	RNase III 2.	might get lost (downstream of altered splice site)
1680	1687	HELIX		might get lost (downstream of altered splice site)
1702	1702	MUTAGEN	Q->A: No effect on activity.	might get lost (downstream of altered splice site)
1702	1722	HELIX		might get lost (downstream of altered splice site)
1705	1705	METAL	Magnesium or manganese 2.	might get lost (downstream of altered splice site)
1709	1709	MUTAGEN	D->A: Decreased activity. Loss of activity; when associated with D-1320.	might get lost (downstream of altered splice site)
1729	1729	MUTAGEN	P->E: No effect on activity.	might get lost (downstream of altered splice site)
1729	1739	HELIX		might get lost (downstream of altered splice site)
1742	1751	HELIX		might get lost (downstream of altered splice site)
1754	1756	HELIX		might get lost (downstream of altered splice site)
1763	1778	HELIX		might get lost (downstream of altered splice site)
1806	1806	SITE	Important for activity (By similarity).	might get lost (downstream of altered splice site)
1806	1822	HELIX		might get lost (downstream of altered splice site)
1810	1810	METAL	Magnesium or manganese 2.	might get lost (downstream of altered splice site)
1813	1813	MUTAGEN	E->A: Decreased activity. Loss of activity; when associated with E-1444.	might get lost (downstream of altered splice site)
1813	1813	METAL	Magnesium or manganese 2.	might get lost (downstream of altered splice site)
1827	1842	HELIX		might get lost (downstream of altered splice site)
1849	1914	DOMAIN	DRBM.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2463 / 2463

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

821 / 821

position of stopcodon in wt / mu cDNA

2746 / 2746

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

284 / 284

chromosome

strand

-1

last intron/exon boundary

2581

theoretical NMD boundary in CDS

2247

length of CDS

2463

coding sequence (CDS) position

1442

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

1725

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

61839

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

95562509

original gDNA sequence snippet

GAGGGCTGCTCAGCTTTTCCTCTGTTCACTGGGGCTGAAGG

altered gDNA sequence snippet

GAGGGCTGCTCAGCTTTTCCGCTGTTCACTGGGGCTGAAGG

original cDNA sequence snippet

GAGGGCTGCTCAGCTTTTCCTCTGTTCACTGGGGCTGAAGG

altered cDNA sequence snippet

GAGGGCTGCTCAGCTTTTCCGCTGTTCACTGGGGCTGAAGG

wildtype AA sequence

MLAWESDHFL RILAENDNYC KHSTIVPENA AHQGANRTSS LENHDQMSVN CRTLLSESPG
KLHVEVSADL TAINGLSYNQ NLANGSYDLA NRDFCQGNQL NYYKQEIPVQ PTTSYSIQNL
YSYENQPQPS DECTLLSNKY LDGNANKSTS DGSPVMAVMP GTTDTIQVLK GRMDSEQSPS
IGYSSRTLGP NPGLILQALT LSNASDGFNL ERLEMLGDSF LKHAITTYLF CTYPDAHEGR
LSYMRSKKVS NCNLYRLGKK KGLPSRMVVS IFDPPVNWLP PGYVVNQDKS NTDKWEKDEM
TKDCMLANGK LDEDYEEEDE EEESLMWRAP KEEADYEDDF LEYDQEHIRF IDNMLMGSGA
FVKKISLSPF STTDSAYEWK MPKKSSLGSM PFSSDFEDFD YSSWDAMCYL DPSKAVEEDD
FVVGFWNPSE ENCGVDTGKQ SISYDLHTEQ CIADKSIADC VEALLGCYLT SCGERAAQLF
LCSLGLKVLP VIKRTDREKA LCPTRENFNS QQKNLSVSCA AASVASSRSS VLKDSEYGCL
KIPPRCMFDH PDADKTLNHL ISGFENFEKK INYRFKNKAY LLQAFTHASY HYNTITDCYQ
RLEFLGDAIL DYLITKHLYE DPRQHSPGVL TDLRSALVNN TIFASLAVKY DYHKYFKAVS
PELFHVIDDF VQFQLEKNEM QGMDSELRRS EEDEEKEEDI EVPKAMGDIF ESLAGAIYMD
SGMSLETVWQ VYYPMMRPLI EKFSANVPRS PVRELLEMEP ETAKFSPAER TYDGKVRVTV
EVVGKGKFKG VGRSYRIAKS AAARRALRSL KANQPQVPNS *

mutated AA sequence

MLAWESDHFL RILAENDNYC KHSTIVPENA AHQGANRTSS LENHDQMSVN CRTLLSESPG
KLHVEVSADL TAINGLSYNQ NLANGSYDLA NRDFCQGNQL NYYKQEIPVQ PTTSYSIQNL
YSYENQPQPS DECTLLSNKY LDGNANKSTS DGSPVMAVMP GTTDTIQVLK GRMDSEQSPS
IGYSSRTLGP NPGLILQALT LSNASDGFNL ERLEMLGDSF LKHAITTYLF CTYPDAHEGR
LSYMRSKKVS NCNLYRLGKK KGLPSRMVVS IFDPPVNWLP PGYVVNQDKS NTDKWEKDEM
TKDCMLANGK LDEDYEEEDE EEESLMWRAP KEEADYEDDF LEYDQEHIRF IDNMLMGSGA
FVKKISLSPF STTDSAYEWK MPKKSSLGSM PFSSDFEDFD YSSWDAMCYL DPSKAVEEDD
FVVGFWNPSE ENCGVDTGKQ SISYDLHTEQ CIADKSIADC VEALLGCYLT SCGERAAQLF
RCSLGLKVLP VIKRTDREKA LCPTRENFNS QQKNLSVSCA AASVASSRSS VLKDSEYGCL
KIPPRCMFDH PDADKTLNHL ISGFENFEKK INYRFKNKAY LLQAFTHASY HYNTITDCYQ
RLEFLGDAIL DYLITKHLYE DPRQHSPGVL TDLRSALVNN TIFASLAVKY DYHKYFKAVS
PELFHVIDDF VQFQLEKNEM QGMDSELRRS EEDEEKEEDI EVPKAMGDIF ESLAGAIYMD
SGMSLETVWQ VYYPMMRPLI EKFSANVPRS PVRELLEMEP ETAKFSPAER TYDGKVRVTV
EVVGKGKFKG VGRSYRIAKS AAARRALRSL KANQPQVPNS *

speed

1.01 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