10-103809082-T-G

Variant names:

• chr10-103809082-T-G
• rs7086883
• NM_001394015.1:c.73-7720A>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.73-7720A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,070 control chromosomes in the GnomAD database, including 8,372 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 0.32 (8372 hom., cov: 31)
• Consequence: SH3PXD2A NM_001394015.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 5 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 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.73-7720A>C		intron	N/A	NP_001380944.1	Q5TCZ1-1
	SH3PXD2A	NM_014631.3		c.73-7720A>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.73-7720A>C		intron	N/A	ENSP00000358789.4	Q5TCZ1-1
	SH3PXD2A	ENST00000355946.7	TSL:1	c.73-7720A>C		intron	N/A	ENSP00000348215.2	Q5TCZ1-3
	SH3PXD2A	ENST00000687380.1		c.73-7720A>C		intron	N/A	ENSP00000508599.1	A0A8I5KQW5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48205 AN: 151952 Hom.: 8360 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.317 AC: 48233 AN: 152070 Hom.: 8372 Cov.: 31 AF XY: 0.313 AC XY: 23282 AN XY: 74334

African (AFR) AF: 0.416 AC: 17240 AN: 41460

American (AMR) AF: 0.205 AC: 3135 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5174

South Asian (SAS) AF: 0.184 AC: 889 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4094 AN: 10576

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20931 AN: 67962

Other (OTH) AF: 0.286 AC: 603 AN: 2112

Alfa AF: 0.304 Hom.: 13413

Bravo AF: 0.306

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.84
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: rs7086883; hg19: chr10-105568840;