rs758284330

chr17-50076635-C-Gchr17-50076635-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002204.4(ITGA3):c.1876C>G(p.Gln626Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27957648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA3	NM_002204.4	c.1876C>G	p.Gln626Glu	missense_variant	14/26	ENST00000320031.13
ITGA3	XM_005257308.3	c.1471C>G	p.Gln491Glu	missense_variant	12/24
ITGA3	XM_047435922.1	c.1876C>G	p.Gln626Glu	missense_variant	14/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA3	ENST00000320031.13	c.1876C>G	p.Gln626Glu	missense_variant	14/26	1	NM_002204.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000808 AC: 2 AN: 247432 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461382 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	0.078
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.14
Sift	Benign	0.067	T;T
Sift4G	Uncertain	0.010	D;D
Polyphen		0.87	P;B
Vest4		0.21
MVP		0.52
MPC		0.41
ClinPred		0.41	T
GERP RS		3.2
Varity_R		0.25
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs758284330; hg19: chr17-48153999;