Variant 10-103602114-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001394015.1(SH3PXD2A):c.3104G>A(p.Arg1035Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,587,978 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0051 ( 33 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 179 hom. )

Consequence

SH3PXD2A
NM_001394015.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.23

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014967918).

BP6

Variant 10-103602114-C-T is Benign according to our data. Variant chr10-103602114-C-T is described in ClinVar as [Benign]. Clinvar id is 708369.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3PXD2A	NM_001394015.1 linkuse as main transcript	c.3104G>A	p.Arg1035Gln	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.3104G>A	p.Arg1035Gln	missense_variant	15/15	5	NM_001394015.1	P4	Q5TCZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

775

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00921

AC:

2146

AN:

232890

Hom.:

AF XY:

0.00819

AC XY:

1024

AN XY:

125028

show subpopulations

Gnomad AFR exome

AF:

0.000752

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0988

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00798

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.00495

GnomAD4 exome

AF:

0.00335

AC:

4807

AN:

1435662

Hom.:

179

Cov.:

AF XY:

0.00328

AC XY:

2327

AN XY:

710332

show subpopulations

Gnomad4 AFR exome

AF:

0.000364

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.000489

Gnomad4 EAS exome

AF:

0.0936

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00725

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00541

GnomAD4 genome

AF:

0.00508

AC:

774

AN:

152316

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00848

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0189

Hom.:

330

Bravo

AF:

0.00496

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00814

AC:

987

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.87

D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.48

T;T

Polyphen

1.0

D;P

Vest4

0.077

MVP

0.68

MPC

1.2

ClinPred

0.014

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.24

gMVP

0.64

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