Genetic Variant SH3PXD2A:p.Ala1024Pro (chr10-103602148-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394015.1(SH3PXD2A):c.3070G>C(p.Ala1024Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 7.0e-7 ( 0 hom. )

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070120305).

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>C	p.Ala1024Pro	missense	Exon 15 of 15	NP_001380944.1	Q5TCZ1-1
SH3PXD2A	NM_014631.3		c.2986G>C	p.Ala996Pro	missense	Exon 14 of 14	NP_055446.2
SH3PXD2A	NM_001365079.1		c.2713G>C	p.Ala905Pro	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>C	p.Ala1024Pro	missense	Exon 15 of 15	ENSP00000358789.4	Q5TCZ1-1
SH3PXD2A	ENST00000355946.7	TSL:1	c.2986G>C	p.Ala996Pro	missense	Exon 14 of 14	ENSP00000348215.2	Q5TCZ1-3
SH3PXD2A	ENST00000315994.6	TSL:1	n.2876G>C		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422662

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702628

show subpopulations

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:

0.0000126

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.011

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.79

M_CAP

Benign

0.029

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-0.0090

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.21

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.31

Polyphen

0.99

Vest4

0.14

MutPred

0.25

Gain of glycosylation at A1024 (P = 0.0461)

MVP

0.54

MPC

1.1

ClinPred

0.58

GERP RS

4.3

Varity_R

0.25

gMVP

0.53

Mutation Taster

=74/26

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