10-103602189-C-T

Variant names:

• chr10-103602189-C-T
• rs576268163
• NM_001394015.1:c.3029G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001394015.1(SH3PXD2A):​c.3029G>A​(p.Arg1010Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000043 in 1,580,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: SH3PXD2A NM_001394015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07035187).
• BS2: High AC in GnomAd4 at 7 AD gene.

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.3029G>A	p.Arg1010Gln	missense	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
	SH3PXD2A	NM_014631.3		c.2945G>A	p.Arg982Gln	missense	Exon 14 of 14	NP_055446.2
	SH3PXD2A	NM_001365079.1		c.2672G>A	p.Arg891Gln	missense	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.3029G>A	p.Arg1010Gln	missense	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
	SH3PXD2A	ENST00000355946.7	TSL:1	c.2945G>A	p.Arg982Gln	missense	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
	SH3PXD2A	ENST00000315994.6	TSL:1	n.2835G>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000889 AC: 20 AN: 224886 AF XY: 0.000100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000986

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000427 AC: 61 AN: 1428648 Hom.: 0 Cov.: 63 AF XY: 0.0000538 AC XY: 38 AN XY: 706180

African (AFR) AF: 0.00 AC: 0 AN: 32876

American (AMR) AF: 0.0000235 AC: 1 AN: 42566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23664

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.000612 AC: 49 AN: 80024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00000549 AC: 6 AN: 1093632

Other (OTH) AF: 0.0000849 AC: 5 AN: 58886

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Benign	0.039	D
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.24		Loss of MoRF binding (P = 0.0162)
MVP		0.72
MPC		1.2
ClinPred		0.31	T
GERP RS		5.3
Varity_R		0.27
gMVP		0.46
Mutation Taster		=51/49	polymorphism

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: rs576268163; hg19: chr10-105361946; COSMIC: COSV100279892;