10-103658043-C-G

Variant names:

• chr10-103658043-C-G
• rs746472
• NM_001394015.1:c.604+2940G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394015.1(SH3PXD2A):​c.604+2940G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,342 control chromosomes in the GnomAD database, including 62,019 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 0.90 (62019 hom., cov: 35)
• Consequence: SH3PXD2A NM_001394015.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2A	NM_001394015.1	c.604+2940G>C		intron_variant	Intron 8 of 14	ENST00000369774.9	NP_001380944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2A	ENST00000369774.9	c.604+2940G>C		intron_variant	Intron 8 of 14	5	NM_001394015.1	ENSP00000358789.4

Frequencies

GnomAD3 genomes AF: 0.900 AC: 137064 AN: 152224 Hom.: 61968 Cov.: 35

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.907

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.900 AC: 137173 AN: 152342 Hom.: 62019 Cov.: 35 AF XY: 0.900 AC XY: 67090 AN XY: 74508

African (AFR) AF: 0.974 AC: 40501 AN: 41584

American (AMR) AF: 0.897 AC: 13735 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3175 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.914 AC: 4413 AN: 4826

European-Finnish (FIN) AF: 0.860 AC: 9133 AN: 10622

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58203 AN: 68030

Other (OTH) AF: 0.907 AC: 1920 AN: 2116

Alfa AF: 0.889 Hom.: 7470

Bravo AF: 0.908

Asia WGS AF: 0.959 AC: 3336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.63
PhyloP100		-0.37
Mutation Taster		=100/0	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: rs746472; hg19: chr10-105417801;