15-68315690-A-G

Position:

• chr15-68315690-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004439.2(ITGA11):​c.2753T>C​(p.Ile918Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ITGA11 NM_001004439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19152108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA11	NM_001004439.2	c.2753T>C	p.Ile918Thr	missense_variant	22/30	ENST00000315757.9	NP_001004439.1
ITGA11	XM_011521363.3	c.2546T>C	p.Ile849Thr	missense_variant	20/28		XP_011519665.1
ITGA11	XM_005254228.4	c.2447T>C	p.Ile816Thr	missense_variant	20/28		XP_005254285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA11	ENST00000315757.9	c.2753T>C	p.Ile918Thr	missense_variant	22/30	1	NM_001004439.2	ENSP00000327290.7
ITGA11	ENST00000423218.6	c.2753T>C	p.Ile918Thr	missense_variant	22/30	2		ENSP00000403392.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ITGA11: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.050	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.072
Sift	Benign	0.39	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	.;B
Vest4		0.37
MutPred		0.44		Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);
MVP		0.72
MPC		0.14
ClinPred		0.35	T
GERP RS		4.8
Varity_R		0.077
gMVP		0.22

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

Other links and lift over

dbSNP: rs1893548743; hg19: chr15-68608028;