rs923799

Positions:

• chr10-103708137-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394015.1(SH3PXD2A):​c.399-15081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,008 control chromosomes in the GnomAD database, including 18,717 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 0.49 (18717 hom., cov: 32)
• Consequence: SH3PXD2A NM_001394015.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3PXD2A	NM_001394015.1	c.399-15081T>C		intron_variant		ENST00000369774.9	NP_001380944.1
SH3PXD2A	NM_014631.3	c.399-15081T>C		intron_variant			NP_055446.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3PXD2A	ENST00000369774.9	c.399-15081T>C		intron_variant		5	NM_001394015.1	ENSP00000358789	P4
SH3PXD2A	ENST00000355946.7	c.399-15081T>C		intron_variant		1		ENSP00000348215	A1
SH3PXD2A	ENST00000687380.1	c.399-15081T>C		intron_variant				ENSP00000508599
SH3PXD2A	ENST00000692756.1	n.256-15081T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74321 AN: 151890 Hom.: 18697 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.489 AC: 74389 AN: 152008 Hom.: 18717 Cov.: 32 AF XY: 0.490 AC XY: 36422 AN XY: 74312

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.478

Alfa AF: 0.442 Hom.: 25631

Bravo AF: 0.498

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.41

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: rs923799; hg19: chr10-105467895;