Variant rs779692470 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5

The NM_000888.5(ITGB6):c.898G>A(p.Glu300Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,455,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ITGB6
NM_000888.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

ITGB6 (HGNC:6161): (integrin subunit beta 6) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ITGB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a domain VWFA (size 240) in uniprot entity ITB6_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_000888.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

PP5

Variant 2-160172592-C-T is Pathogenic according to our data. Variant chr2-160172592-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 217305.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB6	NM_000888.5 linkuse as main transcript	c.898G>A	p.Glu300Lys	missense_variant	6/15	ENST00000283249.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB6	ENST00000283249.7 linkuse as main transcript	c.898G>A	p.Glu300Lys	missense_variant	6/15	1	NM_000888.5	P1	P18564-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251182

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1455588

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

722878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Adolescent alopeciam dentogingival abnormalitites and intellectual disability

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department of Molecular and Human Genetics, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

D;.;.;.;D

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

.;D;D;D;D

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.81

D;D;D;D;D

MetaSVM

Pathogenic

0.96

MutationAssessor

Uncertain

2.1

M;.;.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.0

N;.;N;N;N

REVEL

Pathogenic

0.72

Sift

Benign

0.15

T;.;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

1.0

D;.;D;.;D

Vest4

0.90

MutPred

0.54

Gain of ubiquitination at E300 (P = 0.0162);.;.;Gain of ubiquitination at E300 (P = 0.0162);Gain of ubiquitination at E300 (P = 0.0162);

MVP

0.86

MPC

0.22

ClinPred

0.70

GERP RS

5.5

Varity_R

0.59

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over