10-103601879-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394015.1(SH3PXD2A):c.3339C>G(p.Ile1113Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: SH3PXD2A NM_001394015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.398

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3PXD2A	NM_001394015.1	c.3339C>G	p.Ile1113Met	missense_variant	15/15	ENST00000369774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3PXD2A	ENST00000369774.9	c.3339C>G	p.Ile1113Met	missense_variant	15/15	5	NM_001394015.1	P4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.3255C>G (p.I1085M) alteration is located in exon 14 (coding exon 14) of the SH3PXD2A gene. This alteration results from a C to G substitution at nucleotide position 3255, causing the isoleucine (I) at amino acid position 1085 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.043
Eigen_PC	Benign	0.0083
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.28
Sift	Benign	0.090	T;T
Sift4G	Uncertain	0.010	D;D
Polyphen		0.99	D;D
Vest4		0.59
MutPred		0.53		Gain of catalytic residue at I1113 (P = 0.0826);.;
MVP		0.37
MPC		1.0
ClinPred		0.69	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105361636;