Genetic Variant SH3PXD2A:p.Ala1024Ser (chr10-103602148-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394015.1(SH3PXD2A):c.3070G>T(p.Ala1024Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. A1024T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH3PXD2A
NM_001394015.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

0 publications found

Variant links:

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]

SH3PXD2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06338546).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3PXD2A	NM_001394015.1	MANE Select	c.3070G>T	p.Ala1024Ser	missense	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
SH3PXD2A	NM_014631.3		c.2986G>T	p.Ala996Ser	missense	Exon 14 of 14	NP_055446.2
SH3PXD2A	NM_001365079.1		c.2713G>T	p.Ala905Ser	missense	Exon 9 of 9	NP_001352008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3PXD2A	ENST00000369774.9	TSL:5 MANE Select	c.3070G>T	p.Ala1024Ser	missense	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
SH3PXD2A	ENST00000355946.7	TSL:1	c.2986G>T	p.Ala996Ser	missense	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
SH3PXD2A	ENST00000315994.6	TSL:1	n.2876G>T		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702628

African (AFR)

AF:

0.00

AC:

AN:

32526

American (AMR)

AF:

0.00

AC:

AN:

41428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23358

East Asian (EAS)

AF:

0.00

AC:

AN:

39286

South Asian (SAS)

AF:

0.00

AC:

AN:

79446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090680

Other (OTH)

AF:

0.00

AC:

AN:

58600

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.012

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.041

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-0.0090

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.18

REVEL

Benign

0.075

Sift

Benign

0.31

Sift4G

Benign

0.79

Polyphen

0.81

Vest4

0.059

MutPred

0.28

Gain of phosphorylation at A1024 (P = 0.0034)

MVP

0.52

MPC

0.59

ClinPred

0.72

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.34

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over