chr17-50056473-C-G

Variant names:

• chr17-50056473-C-G
• NM_002204.4:c.34C>G

Variant summary

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

The NM_002204.4(ITGA3):​c.34C>G​(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,140 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: 7.2e-7 (0 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763

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=0.25183347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.34C>G	p.Pro12Ala	missense_variant	Exon 1 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.34C>G	p.Pro12Ala	missense_variant	Exon 1 of 24		XP_005257365.1
ITGA3	XM_047435922.1	c.34C>G	p.Pro12Ala	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.34C>G	p.Pro12Ala	missense_variant	Exon 1 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395140 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688008

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	0.0070	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.24	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.12	T;T
Sift4G	Benign	0.93	T;T
Polyphen		0.018	B;B
Vest4		0.25
MutPred		0.42		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.72
MPC		0.36
ClinPred		0.14	T
GERP RS		5.3
Varity_R		0.065
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: chr17-48133837;