12-55685123-T-G

Position:

• chr12-55685123-T-G

Variant summary

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

The ENST00000257879.11(ITGA7):​c.3349A>C​(p.Ile1117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1117V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA7 ENST00000257879.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 1.43

Genes affected

ITGA7 (HGNC:6143): (integrin subunit alpha 7) The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

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=0.15703204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA7	NM_002206.3	c.3349A>C	p.Ile1117Leu	missense_variant	25/25	ENST00000257879.11	NP_002197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA7	ENST00000257879.11	c.3349A>C	p.Ile1117Leu	missense_variant	25/25	1	NM_002206.3	ENSP00000257879	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Congenital muscular dystrophy due to integrin alpha-7 deficiency Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpretted as Uncertain significance and reported on 05/09/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	.;.;T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	.;.;.;.;L
MutationTaster	Benign	1.0	D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.50	N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.18	B;.;.;B;B
Vest4		0.23
MutPred		0.20		.;.;.;.;Loss of sheet (P = 0.0181);
MVP		0.67
MPC		0.20
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.080
gMVP		0.27

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

Other links and lift over

dbSNP: rs1482793424; hg19: chr12-56078907;