mutation t@sting

Prediction

disease causing

Model: simple_aae, prob: 0.96807216922313 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950473)
known disease mutation: rs16329 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr4:1806153C>AN/A show variant in all transcripts IGV

HGNC symbol

FGFR3

Ensembl transcript ID

ENST00000440486

Genbank transcript ID

NM_000142

UniProt peptide

P22607

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1172C>A
cDNA.1428C>A
g.11120C>A

AA changes

A391E Score: 107 explain score(s)

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

391

frameshift

known variant

Reference ID: rs28931615
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs16329 (pathogenic for Craniosynostosis syndrome|Carcinoma|Crouzon syndrome with acanthosis nigricans|Inborn genetic diseases|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM950473)

known disease mutation at this position, please check HGMD for details (HGMD ID CM950473)
known disease mutation at this position, please check HGMD for details (HGMD ID CM950473)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.611	1
	2.083	0.992
(flanking)	-1.213	0.023

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	11111	wt: 0.9099 / mu: 0.9190 (marginal change - not scored)	wt: GGGCTTCTTCCTGTTCATCCTGGTGGTGGCGGCTGTGACGC mu: GGGCTTCTTCCTGTTCATCCTGGTGGTGGAGGCTGTGACGC	tcct\|GGTG
Acc marginally increased	11110	wt: 0.9510 / mu: 0.9568 (marginal change - not scored)	wt: TGGGCTTCTTCCTGTTCATCCTGGTGGTGGCGGCTGTGACG mu: TGGGCTTCTTCCTGTTCATCCTGGTGGTGGAGGCTGTGACG	atcc\|TGGT
Donor increased	11112	wt: 0.31 / mu: 0.42	wt: ATCCTGGTGGTGGCG mu: ATCCTGGTGGTGGAG	CCTG\|gtgg
Donor marginally increased	11124	wt: 0.9330 / mu: 0.9727 (marginal change - not scored)	wt: GCGGCTGTGACGCTC mu: GAGGCTGTGACGCTC	GGCT\|gtga
Donor gained	11115	0.67	mu: CTGGTGGTGGAGGCT	GGTG\|gtgg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

391

mutated

not conserved

391

Ptroglodytes

all identical

ENSPTRG00000015836

390

Mmulatta

all identical

ENSMMUG00000019945

393

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000054252

387

Ggallus

not conserved

ENSGALG00000015708

389

Trubripes

not conserved

ENSTRUG00000003670

348

Drerio

not conserved

ENSDARG00000004782

386

Dmelanogaster

not conserved

FBgn0010389

324

Celegans

all identical

F58A3.2

539

LFGILF

Xtropicalis

not conserved

ENSXETG00000002396

409

protein features

start (aa)	end (aa)	feature	details
376	396	TRANSMEM	Helical; (Potential).	lost
395	395	CONFLICT	L -> V (in Ref. 7; AAA58470).	might get lost (downstream of altered splice site)
397	806	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
421	421	CONFLICT	R -> RQ (in Ref. 3; BAD92678).	might get lost (downstream of altered splice site)
472	761	DOMAIN	Protein kinase.	might get lost (downstream of altered splice site)
478	486	NP_BIND	ATP (By similarity).	might get lost (downstream of altered splice site)
508	508	MUTAGEN	K->A: Loss of kinase activity. Abolishes ubiquitination.	might get lost (downstream of altered splice site)
508	508	BINDING	ATP (By similarity).	might get lost (downstream of altered splice site)
577	577	MUTAGEN	Y->F: Minor effect on kinase activity.	might get lost (downstream of altered splice site)
617	617	ACT_SITE	Proton acceptor (By similarity).	might get lost (downstream of altered splice site)
647	647	MOD_RES	Phosphotyrosine; by autocatalysis.	might get lost (downstream of altered splice site)
648	648	MOD_RES	Phosphotyrosine; by autocatalysis.	might get lost (downstream of altered splice site)
724	724	MUTAGEN	Y->F: Strongly reduced kinase activity. Strongly reduced mitogen activity.	might get lost (downstream of altered splice site)
724	724	MOD_RES	Phosphotyrosine; by autocatalysis.	might get lost (downstream of altered splice site)
760	760	MUTAGEN	Y->F: Minor effect on kinase activity.	might get lost (downstream of altered splice site)
760	760	MOD_RES	Phosphotyrosine; by autocatalysis.	might get lost (downstream of altered splice site)
770	770	MUTAGEN	Y->F: Minor effect on kinase activity. Increased mitogen activity.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2421 / 2421

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

807 / 807

position of stopcodon in wt / mu cDNA

2677 / 2677

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

257 / 257

chromosome

strand

last intron/exon boundary

2531

theoretical NMD boundary in CDS

2224

length of CDS

2421

coding sequence (CDS) position

1172

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

1428

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

11120

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

1806153

original gDNA sequence snippet

CCTGTTCATCCTGGTGGTGGCGGCTGTGACGCTCTGCCGCC

altered gDNA sequence snippet

CCTGTTCATCCTGGTGGTGGAGGCTGTGACGCTCTGCCGCC

original cDNA sequence snippet

CCTGTTCATCCTGGTGGTGGCGGCTGTGACGCTCTGCCGCC

altered cDNA sequence snippet

CCTGTTCATCCTGGTGGTGGAGGCTGTGACGCTCTGCCGCC

wildtype AA sequence

MGAPACALAL CVAVAIVAGA SSESLGTEQR VVGRAAEVPG PEPGQQEQLV FGSGDAVELS
CPPPGGGPMG PTVWVKDGTG LVPSERVLVG PQRLQVLNAS HEDSGAYSCR QRLTQRVLCH
FSVRVTDAPS SGDDEDGEDE AEDTGVDTGA PYWTRPERMD KKLLAVPAAN TVRFRCPAAG
NPTPSISWLK NGREFRGEHR IGGIKLRHQQ WSLVMESVVP SDRGNYTCVV ENKFGSIRQT
YTLDVLERSP HRPILQAGLP ANQTAVLGSD VEFHCKVYSD AQPHIQWLKH VEVNGSKVGP
DGTPYVTVLK TAGANTTDKE LEVLSLHNVT FEDAGEYTCL AGNSIGFSHH SAWLVVLPAE
EELVEADEAG SVYAGILSYG VGFFLFILVV AAVTLCRLRS PPKKGLGSPT VHKISRFPLK
RQVSLESNAS MSSNTPLVRI ARLSSGEGPT LANVSELELP ADPKWELSRA RLTLGKPLGE
GCFGQVVMAE AIGIDKDRAA KPVTVAVKML KDDATDKDLS DLVSEMEMMK MIGKHKNIIN
LLGACTQGGP LYVLVEYAAK GNLREFLRAR RPPGLDYSFD TCKPPEEQLT FKDLVSCAYQ
VARGMEYLAS QKCIHRDLAA RNVLVTEDNV MKIADFGLAR DVHNLDYYKK TTNGRLPVKW
MAPEALFDRV YTHQSDVWSF GVLLWEIFTL GGSPYPGIPV EELFKLLKEG HRMDKPANCT
HDLYMIMREC WHAAPSQRPT FKQLVEDLDR VLTVTSTDEY LDLSAPFEQY SPGGQDTPSS
SSSGDDSVFA HDLLPPAPPS SGGSRT*

mutated AA sequence

MGAPACALAL CVAVAIVAGA SSESLGTEQR VVGRAAEVPG PEPGQQEQLV FGSGDAVELS
CPPPGGGPMG PTVWVKDGTG LVPSERVLVG PQRLQVLNAS HEDSGAYSCR QRLTQRVLCH
FSVRVTDAPS SGDDEDGEDE AEDTGVDTGA PYWTRPERMD KKLLAVPAAN TVRFRCPAAG
NPTPSISWLK NGREFRGEHR IGGIKLRHQQ WSLVMESVVP SDRGNYTCVV ENKFGSIRQT
YTLDVLERSP HRPILQAGLP ANQTAVLGSD VEFHCKVYSD AQPHIQWLKH VEVNGSKVGP
DGTPYVTVLK TAGANTTDKE LEVLSLHNVT FEDAGEYTCL AGNSIGFSHH SAWLVVLPAE
EELVEADEAG SVYAGILSYG VGFFLFILVV EAVTLCRLRS PPKKGLGSPT VHKISRFPLK
RQVSLESNAS MSSNTPLVRI ARLSSGEGPT LANVSELELP ADPKWELSRA RLTLGKPLGE
GCFGQVVMAE AIGIDKDRAA KPVTVAVKML KDDATDKDLS DLVSEMEMMK MIGKHKNIIN
LLGACTQGGP LYVLVEYAAK GNLREFLRAR RPPGLDYSFD TCKPPEEQLT FKDLVSCAYQ
VARGMEYLAS QKCIHRDLAA RNVLVTEDNV MKIADFGLAR DVHNLDYYKK TTNGRLPVKW
MAPEALFDRV YTHQSDVWSF GVLLWEIFTL GGSPYPGIPV EELFKLLKEG HRMDKPANCT
HDLYMIMREC WHAAPSQRPT FKQLVEDLDR VLTVTSTDEY LDLSAPFEQY SPGGQDTPSS
SSSGDDSVFA HDLLPPAPPS SGGSRT*

speed

0.90 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