Genetic Variant SH3PXD2A:p.Arg932Arg (chr10-103602422-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001394015.1(SH3PXD2A):c.2796C>T(p.Arg932Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 1,613,918 control chromosomes in the GnomAD database, including 7,592 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 814 hom., cov: 33)

Exomes 𝑓: 0.088 ( 6778 hom. )

Consequence

SH3PXD2A
NM_001394015.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.753

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.043).

BP7

Synonymous conserved (PhyloP=-0.753 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2A	NM_001394015.1 link	c.2796C>T	p.Arg932Arg	synonymous_variant	Exon 15 of 15	ENST00000369774.9	NP_001380944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2A	ENST00000369774.9 link	c.2796C>T	p.Arg932Arg	synonymous_variant	Exon 15 of 15	5	NM_001394015.1	ENSP00000358789.4		Q5TCZ1-1

Frequencies

GnomAD3 genomes

AF:

0.0976

AC:

14849

AN:

152064

Hom.:

811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.0901

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.0972

AC:

24411

AN:

251072

AF XY:

0.0941

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.0946

Gnomad EAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.0937

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.0882

AC:

128990

AN:

1461736

Hom.:

6778

Cov.:

AF XY:

0.0873

AC XY:

63504

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.0985

AC:

3296

AN:

33478

American (AMR)

AF:

0.0747

AC:

3341

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0923

AC:

2413

AN:

26134

East Asian (EAS)

AF:

0.254

AC:

10097

AN:

39698

South Asian (SAS)

AF:

0.0463

AC:

3997

AN:

86258

European-Finnish (FIN)

AF:

0.138

AC:

7336

AN:

53352

Middle Eastern (MID)

AF:

0.122

AC:

705

AN:

5768

European-Non Finnish (NFE)

AF:

0.0831

AC:

92413

AN:

1111936

Other (OTH)

AF:

0.0893

AC:

5392

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

7347

14695

22042

29390

36737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3362

6724

10086

13448

16810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0977

AC:

14869

AN:

152182

Hom.:

814

Cov.:

AF XY:

0.0987

AC XY:

7343

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0956

AC:

3969

AN:

41530

American (AMR)

AF:

0.0925

AC:

1414

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

310

AN:

3470

East Asian (EAS)

AF:

0.212

AC:

1091

AN:

5158

South Asian (SAS)

AF:

0.0414

AC:

200

AN:

4828

European-Finnish (FIN)

AF:

0.140

AC:

1485

AN:

10592

Middle Eastern (MID)

AF:

0.0993

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0901

AC:

6129

AN:

68000

Other (OTH)

AF:

0.100

AC:

211

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

691

1382

2074

2765

3456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0946

Hom.:

752

Bravo

AF:

0.0971

Asia WGS

AF:

0.109

AC:

380

AN:

3478

EpiCase

AF:

0.0971

EpiControl

AF:

0.0883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.82

(source)

DANN

Benign

0.46

PhyloP100

-0.75

Mutation Taster

=97/3

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over