Genetic Variant ITGA7:p.Arg43Pro (chr12-55707555-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002206.3(ITGA7):c.128G>C(p.Arg43Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

ITGA7
NM_002206.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.223

Publications

1 publications found

Variant links:

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]

ITGA7 Gene-Disease associations (from GenCC):

congenital muscular dystrophy due to integrin alpha-7 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ITGA7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002206.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA7	NM_002206.3	MANE Select	c.128G>C	p.Arg43Pro	missense	Exon 1 of 25	NP_002197.2	Q13683-7
ITGA7	NM_001410977.1		c.128G>C	p.Arg43Pro	missense	Exon 1 of 26	NP_001397906.1	Q13683-1
ITGA7	NM_001144996.2		c.128G>C	p.Arg43Pro	missense	Exon 1 of 25	NP_001138468.1	Q13683-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA7	ENST00000257879.11	TSL:1 MANE Select	c.128G>C	p.Arg43Pro	missense	Exon 1 of 25	ENSP00000257879.7	Q13683-7
ITGA7	ENST00000553804.6	TSL:1	c.128G>C	p.Arg43Pro	missense	Exon 1 of 25	ENSP00000452120.1	Q13683-3
ITGA7	ENST00000555728.5	TSL:5	c.128G>C	p.Arg43Pro	missense	Exon 1 of 26	ENSP00000452387.1	Q13683-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.52

MetaRNN

Uncertain

0.64

MetaSVM

Uncertain

-0.078

MutationAssessor

Uncertain

2.7

PhyloP100

-0.22

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.57

Sift

Uncertain

0.026

Sift4G

Benign

0.20

Polyphen

0.84

Vest4

0.68

MutPred

0.52

Loss of sheet (P = 0.0315)

MVP

0.88

MPC

0.52

ClinPred

0.91

GERP RS

1.4

PromoterAI

-0.085

Neutral

(source)

Varity_R

0.64

gMVP

0.72

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over