Variant 10-103602184-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001394015.1(SH3PXD2A):c.3034G>A(p.Val1012Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00108 in 1,575,330 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 6 hom. )

Consequence

SH3PXD2A
NM_001394015.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.87

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00867787).

BP6

Variant 10-103602184-C-T is Benign according to our data. Variant chr10-103602184-C-T is described in ClinVar as [Benign]. Clinvar id is 717164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00523 (797/152276) while in subpopulation AFR AF= 0.0179 (745/41564). AF 95% confidence interval is 0.0169. There are 10 homozygotes in gnomad4. There are 348 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3PXD2A	NM_001394015.1 linkuse as main transcript	c.3034G>A	p.Val1012Ile	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.3034G>A	p.Val1012Ile	missense_variant	15/15	5	NM_001394015.1	P4	Q5TCZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00171

AC:

376

AN:

220344

Hom.:

AF XY:

0.00125

AC XY:

147

AN XY:

117506

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000675

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000630

AC:

897

AN:

1423054

Hom.:

Cov.:

AF XY:

0.000546

AC XY:

384

AN XY:

702890

show subpopulations

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000458

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00523

AC:

797

AN:

152276

Hom.:

Cov.:

AF XY:

0.00467

AC XY:

348

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00617

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00190

AC:

230

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.15

Sift

Benign

0.045

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;D

Vest4

0.25

MVP

0.74

MPC

0.97

ClinPred

0.015

GERP RS

5.3

Varity_R

0.14

gMVP

0.39

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