rs3740473

chr10-103602422-G-Achr10-103602422-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001394015.1(SH3PXD2A):c.2796C>T(p.Arg932=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 1,613,918 control chromosomes in the GnomAD database, including 7,592 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.098 (814 hom., cov: 33)
  • Exomes 𝑓: 0.088 (6778 hom.)
• Consequence: SH3PXD2A NM_001394015.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

Genes affected

SH3PXD2A (HGNC:23664): (SH3 and PX domains 2A) Predicted to enable superoxide-generating NADPH oxidase activator activity. Involved in osteoclast fusion and superoxide metabolic process. Located in podosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.753 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3PXD2A	NM_001394015.1	c.2796C>T	p.Arg932=	synonymous_variant	15/15	ENST00000369774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3PXD2A	ENST00000369774.9	c.2796C>T	p.Arg932=	synonymous_variant	15/15	5	NM_001394015.1	P4

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14849 AN: 152064 Hom.: 811 Cov.: 33

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0972 AC: 24411 AN: 251072 Hom.: 1412 AF XY: 0.0941 AC XY: 12780 AN XY: 135762

Gnomad AFR exome AF: 0.0925

Gnomad AMR exome AF: 0.0731

Gnomad ASJ exome AF: 0.0946

Gnomad EAS exome AF: 0.206

Gnomad SAS exome AF: 0.0433

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.0937

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0882 AC: 128990 AN: 1461736 Hom.: 6778 Cov.: 63 AF XY: 0.0873 AC XY: 63504 AN XY: 727180

Gnomad4 AFR exome AF: 0.0985

Gnomad4 AMR exome AF: 0.0747

Gnomad4 ASJ exome AF: 0.0923

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.0463

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0831

Gnomad4 OTH exome AF: 0.0893

GnomAD4 genome AF: 0.0977 AC: 14869 AN: 152182 Hom.: 814 Cov.: 33 AF XY: 0.0987 AC XY: 7343 AN XY: 74398

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.0925

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.0414

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0901

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0927 Hom.: 310

Bravo AF: 0.0971

Asia WGS AF: 0.109 AC: 380 AN: 3478

EpiCase AF: 0.0971

EpiControl AF: 0.0883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.82
Dann	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs3740473; hg19: chr10-105362179; COSMIC: COSV100279884;