17-50056516-G-C

Variant names:

• chr17-50056516-G-C
• NM_002204.4:c.77G>C

Variant summary

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

The NM_002204.4(ITGA3):​c.77G>C​(p.Gly26Ala) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

ITGA3 (HGNC:6139): (integrin subunit alpha 3) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function as cell surface adhesion molecules. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 3 subunit. This subunit joins with a beta 1 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. Expression of this gene may be correlated with breast cancer metastasis. [provided by RefSeq, Oct 2015]

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=0.110328734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 24		XP_005257365.1
ITGA3	XM_047435922.1	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 18		XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.77G>C	p.Gly26Ala	missense_variant	Exon 1 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jun 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with ITGA3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 26 of the ITGA3 protein (p.Gly26Ala). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.23
Sift	Benign	0.82	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.20
MutPred		0.48		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.66
MPC		0.40
ClinPred		0.17	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-48133880;