rs201558536

Variant names:

• chr10-103601968-C-G
• rs201558536
• NM_001394015.1:c.3250G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-103601968-C-G
• chr10-103601968-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394015.1(SH3PXD2A):​c.3250G>C​(p.Glu1084Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1084K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: SH3PXD2A NM_001394015.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39262575).

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.3250G>C	p.Glu1084Gln	missense	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
	SH3PXD2A	NM_014631.3		c.3166G>C	p.Glu1056Gln	missense	Exon 14 of 14	NP_055446.2
	SH3PXD2A	NM_001365079.1		c.2893G>C	p.Glu965Gln	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.3250G>C	p.Glu1084Gln	missense	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
	SH3PXD2A	ENST00000355946.7	TSL:1	c.3166G>C	p.Glu1056Gln	missense	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
	SH3PXD2A	ENST00000315994.6	TSL:1	n.3056G>C		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.63	N
PhyloP100		6.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.29
Sift	Benign	0.26	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.50		Loss of disorder (P = 0.095)
MVP		0.52
MPC		1.1
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.48
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201558536; hg19: chr10-105361725;