Variant 15-68313782-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004439.2(ITGA11):c.2879C>T(p.Thr960Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,613,506 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

ITGA11
NM_001004439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94

Variant links:

Genes affected

ITGA11 (HGNC:6136): (integrin subunit alpha 11) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein contains an I domain, is expressed in muscle tissue, dimerizes with beta 1 integrin in vitro, and appears to bind collagen in this form. Therefore, the protein may be involved in attaching muscle tissue to the extracellular matrix. Alternative transcriptional splice variants have been found for this gene, but their biological validity is not determined. [provided by RefSeq, Jul 2008]

ITGA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA11	NM_001004439.2 link	c.2879C>T	p.Thr960Ile	missense_variant	23/30	ENST00000315757.9	NP_001004439.1	Q9UKX5-1B3KTN6
ITGA11	XM_011521363.3 link	c.2672C>T	p.Thr891Ile	missense_variant	21/28		XP_011519665.1
ITGA11	XM_005254228.4 link	c.2573C>T	p.Thr858Ile	missense_variant	21/28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9 link	c.2879C>T	p.Thr960Ile	missense_variant	23/30	1	NM_001004439.2	ENSP00000327290.7		Q9UKX5-1
ITGA11	ENST00000423218.6 link	c.2879C>T	p.Thr960Ile	missense_variant	23/30	2		ENSP00000403392.2		Q9UKX5-2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000197

AC:

AN:

248320

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000409

AC:

597

AN:

1461280

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

295

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000515

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000243

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000357

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.000482

AC:

ExAC

AF:

0.000207

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.2879C>T (p.T960I) alteration is located in exon 23 (coding exon 23) of the ITGA11 gene. This alteration results from a C to T substitution at nucleotide position 2879, causing the threonine (T) at amino acid position 960 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.35

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

.;D

Vest4

0.90

MVP

0.89

MPC

0.55

ClinPred

0.49

GERP RS

4.9

Varity_R

0.36

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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