Variant 15-68311031-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004439.2(ITGA11):c.3137C>A(p.Thr1046Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,607,264 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ITGA11
NM_001004439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051722437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA11	NM_001004439.2 link	c.3137C>A	p.Thr1046Asn	missense_variant	26/30	ENST00000315757.9	NP_001004439.1	Q9UKX5-1B3KTN6
ITGA11	XM_011521363.3 link	c.2930C>A	p.Thr977Asn	missense_variant	24/28		XP_011519665.1
ITGA11	XM_005254228.4 link	c.2831C>A	p.Thr944Asn	missense_variant	24/28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9 link	c.3137C>A	p.Thr1046Asn	missense_variant	26/30	1	NM_001004439.2	ENSP00000327290.7		Q9UKX5-1
ITGA11	ENST00000423218.6 link	c.3140C>A	p.Thr1047Asn	missense_variant	26/30	2		ENSP00000403392.2		Q9UKX5-2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000506

AC:

AN:

236920

Hom.:

AF XY:

0.0000467

AC XY:

AN XY:

128400

show subpopulations

Gnomad AFR exome

AF:

0.000797

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1454902

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

722940

show subpopulations

Gnomad4 AFR exome

AF:

0.000600

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.000223

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000572

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000482

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

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

Dec 18, 2023

The c.3137C>A (p.T1046N) alteration is located in exon 26 (coding exon 26) of the ITGA11 gene. This alteration results from a C to A substitution at nucleotide position 3137, causing the threonine (T) at amino acid position 1046 to be replaced by an asparagine (N). 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

Benign

0.070

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.10

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.058

Sift

Benign

0.55

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.055

.;B

Vest4

0.25

MVP

0.48

MPC

0.13

ClinPred

0.014

GERP RS

2.8

Varity_R

0.033

gMVP

0.30

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