Variant 10-103602154-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394015.1(SH3PXD2A):c.3064C>T(p.Arg1022Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,575,472 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1022H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 12 hom. )

Consequence

SH3PXD2A
NM_001394015.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.68

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007769078).

BP6

Variant 10-103602154-G-A is Benign according to our data. Variant chr10-103602154-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720165.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 649 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3PXD2A	NM_001394015.1 linkuse as main transcript	c.3064C>T	p.Arg1022Cys	missense_variant	15/15	ENST00000369774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3PXD2A	ENST00000369774.9 linkuse as main transcript	c.3064C>T	p.Arg1022Cys	missense_variant	15/15	5	NM_001394015.1	P4	Q5TCZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

649

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00498

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00347

AC:

764

AN:

220252

Hom.:

AF XY:

0.00333

AC XY:

391

AN XY:

117330

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000337

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.00302

Gnomad NFE exome

AF:

0.00484

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00435

AC:

6193

AN:

1423164

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

3012

AN XY:

702902

show subpopulations

Gnomad4 AFR exome

AF:

0.00568

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.000128

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.000944

Gnomad4 FIN exome

AF:

0.00313

Gnomad4 NFE exome

AF:

0.00497

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152308

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00532

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.00420

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00336

AC:

407

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;D

Vest4

0.36

MVP

0.67

MPC

1.2

ClinPred

0.027

GERP RS

4.3

Varity_R

0.17

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over