Variant 15-68311073-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004439.2(ITGA11):c.3095C>T(p.Thr1032Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,454,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ITGA11
NM_001004439.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35351902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA11	NM_001004439.2 link	c.3095C>T	p.Thr1032Met	missense_variant	26/30	ENST00000315757.9	NP_001004439.1	Q9UKX5-1B3KTN6
ITGA11	XM_011521363.3 link	c.2888C>T	p.Thr963Met	missense_variant	24/28		XP_011519665.1
ITGA11	XM_005254228.4 link	c.2789C>T	p.Thr930Met	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.3095C>T	p.Thr1032Met	missense_variant	26/30	1	NM_001004439.2	ENSP00000327290.7		Q9UKX5-1
ITGA11	ENST00000423218.6 link	c.3098C>T	p.Thr1033Met	missense_variant	26/30	2		ENSP00000403392.2		Q9UKX5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000295

AC:

AN:

237400

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

128562

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:

0.0000696

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1454722

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722918

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:

0.0000708

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000496

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

Apr 05, 2023

The c.3095C>T (p.T1032M) alteration is located in exon 26 (coding exon 26) of the ITGA11 gene. This alteration results from a C to T substitution at nucleotide position 3095, causing the threonine (T) at amino acid position 1032 to be replaced by a methionine (M). 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

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

.;T

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.41

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.58

.;P

Vest4

0.36

MutPred

0.58

.;Gain of catalytic residue at T1032 (P = 0.0031);

MVP

0.77

MPC

0.13

ClinPred

0.18

GERP RS

4.0

Varity_R

0.044

gMVP

0.57

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