rs3740473

Variant names:

• chr10-103602422-G-A
• rs3740473
• NM_001394015.1:c.2796C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103602422-G-A
• chr10-103602422-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001394015.1(SH3PXD2A):​c.2796C>T​(p.Arg932Arg) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.043).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394015.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2A	NM_001394015.1	MANE Select	c.2796C>T	p.Arg932Arg	synonymous	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
	SH3PXD2A	NM_014631.3		c.2712C>T	p.Arg904Arg	synonymous	Exon 14 of 14	NP_055446.2
	SH3PXD2A	NM_001365079.1		c.2439C>T	p.Arg813Arg	synonymous	Exon 9 of 9	NP_001352008.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2A	ENST00000369774.9	TSL:5 MANE Select	c.2796C>T	p.Arg932Arg	synonymous	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
	SH3PXD2A	ENST00000355946.7	TSL:1	c.2712C>T	p.Arg904Arg	synonymous	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
	SH3PXD2A	ENST00000315994.6	TSL:1	n.2602C>T		non_coding_transcript_exon	Exon 12 of 12

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

GnomAD2 exomes AF: 0.0972 AC: 24411 AN: 251072 AF XY: 0.0941

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 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

African (AFR) AF: 0.0985 AC: 3296 AN: 33478

American (AMR) AF: 0.0747 AC: 3341 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 2413 AN: 26134

East Asian (EAS) AF: 0.254 AC: 10097 AN: 39698

South Asian (SAS) AF: 0.0463 AC: 3997 AN: 86258

European-Finnish (FIN) AF: 0.138 AC: 7336 AN: 53352

Middle Eastern (MID) AF: 0.122 AC: 705 AN: 5768

European-Non Finnish (NFE) AF: 0.0831 AC: 92413 AN: 1111936

Other (OTH) AF: 0.0893 AC: 5392 AN: 60390

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

African (AFR) AF: 0.0956 AC: 3969 AN: 41530

American (AMR) AF: 0.0925 AC: 1414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1091 AN: 5158

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1485 AN: 10592

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0901 AC: 6129 AN: 68000

Other (OTH) AF: 0.100 AC: 211 AN: 2108

Alfa AF: 0.0946 Hom.: 752

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.82
DANN	Benign	0.46
PhyloP100		-0.75
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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