rs923799

Variant names:

• chr10-103708137-A-G
• rs923799
• NM_001394015.1:c.399-15081T>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.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
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 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.399-15081T>C		intron	N/A	NP_001380944.1	Q5TCZ1-1
	SH3PXD2A	NM_014631.3		c.399-15081T>C		intron	N/A	NP_055446.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2A	ENST00000369774.9	TSL:5 MANE Select	c.399-15081T>C		intron	N/A	ENSP00000358789.4	Q5TCZ1-1
	SH3PXD2A	ENST00000355946.7	TSL:1	c.399-15081T>C		intron	N/A	ENSP00000348215.2	Q5TCZ1-3
	SH3PXD2A	ENST00000687380.1		c.399-15081T>C		intron	N/A	ENSP00000508599.1	A0A8I5KQW5

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

African (AFR) AF: 0.608 AC: 25203 AN: 41432

American (AMR) AF: 0.449 AC: 6859 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1405 AN: 3462

East Asian (EAS) AF: 0.605 AC: 3125 AN: 5164

South Asian (SAS) AF: 0.358 AC: 1723 AN: 4816

European-Finnish (FIN) AF: 0.501 AC: 5291 AN: 10570

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29353 AN: 67960

Other (OTH) AF: 0.478 AC: 1008 AN: 2110

Alfa AF: 0.450 Hom.: 61354

Bravo AF: 0.498

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.41
PhyloP100		-0.11
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: rs923799; hg19: chr10-105467895;