17-50056470-G-A

Position:

• chr17-50056470-G-A

Variant summary

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

The NM_002204.4(ITGA3):​c.31G>A​(p.Ala11Thr) 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. 13/21 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: 1.94

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=0.20405924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.31G>A	p.Ala11Thr	missense_variant	1/26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.31G>A	p.Ala11Thr	missense_variant	1/24		XP_005257365.1
ITGA3	XM_047435922.1	c.31G>A	p.Ala11Thr	missense_variant	1/18		XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.31G>A	p.Ala11Thr	missense_variant	1/26	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

Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.12
Sift	Benign	0.15	T;T
Sift4G	Benign	0.068	T;T
Polyphen		0.0080	B;B
Vest4		0.11
MutPred		0.32		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.76
MPC		0.36
ClinPred		0.16	T
GERP RS		3.2
Varity_R		0.068
gMVP		0.34

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: chr17-48133834;