mutation t@sting

Prediction

disease causing

Model: simple_aae, prob: 0.999999999975379 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM1212976)
known disease mutation at this position (HGMD CM970636)
known disease mutation: rs36243 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr7:44189362C>TN/A show variant in all transcripts IGV

HGNC symbol

GCK

Ensembl transcript ID

ENST00000403799

Genbank transcript ID

NM_000162

UniProt peptide

P35557

alteration type

single base exchange

alteration region

CDS

DNA changes

c.676G>A
cDNA.1146G>A
g.48408G>A

AA changes

V226M Score: 21 explain score(s)

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

226

frameshift

known variant

Reference ID: rs148311934

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	1	1

known disease mutation: rs36243 (pathogenic for Maturity onset diabetes mellitus in young|Type 2 diabetes mellitus|Maturity-onset diabetes of the young, type 2|Hyperinsulinism due to glucokinase deficiency|Permanent neonatal diabetes mellitus|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM970636)

known disease mutation at this position, please check HGMD for details (HGMD ID CM970636)
known disease mutation at this position, please check HGMD for details (HGMD ID CM1212976)

known disease mutation at this position, please check HGMD for details (HGMD ID CM970636)
known disease mutation at this position, please check HGMD for details (HGMD ID CM1212976)
known disease mutation at this position, please check HGMD for details (HGMD ID CM970636)

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.232	1
	6.337	1
(flanking)	-0.112	0.979

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

splice sites

alteration within used splice site, likely to disturb normal splicing

effect	gDNA position	score	detection sequence	exon-intron border
Donor lost	48411	sequence motif lost	-	wt: GTGG\|gtaa mu: ATGG.gtaa
Donor marginally increased	48410	wt: 0.9769 / mu: 0.9930 (marginal change - not scored)	wt: ATCGTGGGTAAGGGC mu: ATCATGGGTAAGGGC	CGTG\|ggta

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

226

mutated

all conserved

226

Ptroglodytes

all identical

ENSPTRG00000019140

225

Mmulatta

all identical

ENSMMUG00000002427

227

Fcatus

all identical

ENSFCAG00000014361

211

Mmusculus

all identical

ENSMUSG00000041798

226

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000068006

236

Dmelanogaster

all identical

FBgn0001186

301

Celegans

all identical

F14B4.2

244

Xtropicalis

all identical

ENSXETG00000019003

226

protein features

start (aa)	end (aa)	feature	details
220	237	STRAND		lost
228	228	BINDING	ATP (By similarity).	might get lost (downstream of altered splice site)
231	231	BINDING	Substrate.	might get lost (downstream of altered splice site)
238	240	HELIX		might get lost (downstream of altered splice site)
248	254	STRAND		might get lost (downstream of altered splice site)
256	256	BINDING	Substrate.	might get lost (downstream of altered splice site)
256	256	MUTAGEN	E->A: Inactive enzyme.	might get lost (downstream of altered splice site)
257	259	HELIX		might get lost (downstream of altered splice site)
260	263	TURN		might get lost (downstream of altered splice site)
267	269	HELIX		might get lost (downstream of altered splice site)
272	280	HELIX		might get lost (downstream of altered splice site)
281	283	STRAND		might get lost (downstream of altered splice site)
288	291	HELIX		might get lost (downstream of altered splice site)
290	290	BINDING	Substrate.	might get lost (downstream of altered splice site)
295	296	NP_BIND	ATP (By similarity).	might get lost (downstream of altered splice site)
295	311	HELIX		might get lost (downstream of altered splice site)
316	318	HELIX		might get lost (downstream of altered splice site)
322	325	TURN		might get lost (downstream of altered splice site)
332	336	NP_BIND	ATP (By similarity).	might get lost (downstream of altered splice site)
332	339	HELIX		might get lost (downstream of altered splice site)
340	342	STRAND		might get lost (downstream of altered splice site)
343	345	STRAND		might get lost (downstream of altered splice site)
346	354	HELIX		might get lost (downstream of altered splice site)
361	396	HELIX		might get lost (downstream of altered splice site)
400	409	STRAND		might get lost (downstream of altered splice site)
411	415	NP_BIND	ATP (By similarity).	might get lost (downstream of altered splice site)
411	415	HELIX		might get lost (downstream of altered splice site)
414	414	MUTAGEN	K->A: Small change in activity.	might get lost (downstream of altered splice site)
416	418	STRAND		might get lost (downstream of altered splice site)
419	430	HELIX		might get lost (downstream of altered splice site)
434	440	STRAND		might get lost (downstream of altered splice site)
444	456	HELIX		might get lost (downstream of altered splice site)
457	459	TURN		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1398 / 1398

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

466 / 466

position of stopcodon in wt / mu cDNA

1868 / 1868

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

471 / 471

chromosome

strand

-1

last intron/exon boundary

1724

theoretical NMD boundary in CDS

1203

length of CDS

1398

coding sequence (CDS) position

676

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

1146

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

48408

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

44189362

original gDNA sequence snippet

AGTGCGAGGTCGGCATGATCGTGGGTAAGGGCTCCTTGCAC

altered gDNA sequence snippet

AGTGCGAGGTCGGCATGATCATGGGTAAGGGCTCCTTGCAC

original cDNA sequence snippet

AGTGCGAGGTCGGCATGATCGTGGGCACGGGCTGCAATGCC

altered cDNA sequence snippet

AGTGCGAGGTCGGCATGATCATGGGCACGGGCTGCAATGCC

wildtype AA sequence

MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT
YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE
MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN
VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN
VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS
TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK
ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ*

mutated AA sequence

MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT
YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE
MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN
VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIMGTGC NACYMEEMQN
VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS
TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK
ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ*

speed

0.97 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