Variant rs13356223 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_001017995.3(SH3PXD2B):c.233-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,612,208 control chromosomes in the GnomAD database, including 1,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.062 ( 433 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1222 hom. )

Consequence

SH3PXD2B
NM_001017995.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.439

Variant links:

Genes affected

SH3PXD2B (HGNC:29242): (SH3 and PX domains 2B) This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SH3PXD2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-172394667-T-C is Benign according to our data. Variant chr5-172394667-T-C is described in ClinVar as [Benign]. Clinvar id is 1249452.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SH3PXD2B	NM_001017995.3 linkuse as main transcript	c.233-28A>G	intron_variant	ENST00000311601.6
SH3PXD2B	NM_001308175.2 linkuse as main transcript	c.233-28A>G	intron_variant
SH3PXD2B	XM_017009351.2 linkuse as main transcript	c.233-28A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
SH3PXD2B	ENST00000311601.6 linkuse as main transcript	c.233-28A>G	intron_variant	1	NM_001017995.3	P1
SH3PXD2B	ENST00000519643.5 linkuse as main transcript	c.233-28A>G	intron_variant	1
SH3PXD2B	ENST00000636523.1 linkuse as main transcript	c.189-28A>G	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9363

AN:

152126

Hom.:

431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00975

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0597

GnomAD3 exomes

AF:

0.0357

AC:

8921

AN:

249958

Hom.:

282

AF XY:

0.0333

AC XY:

4493

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0662

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0365

Gnomad OTH exome

AF:

0.0371

GnomAD4 exome

AF:

0.0358

AC:

52270

AN:

1459962

Hom.:

1222

Cov.:

AF XY:

0.0347

AC XY:

25182

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0315

Gnomad4 NFE exome

AF:

0.0356

Gnomad4 OTH exome

AF:

0.0430

GnomAD4 genome

AF:

0.0616

AC:

9379

AN:

152246

Hom.:

433

Cov.:

AF XY:

0.0582

AC XY:

4336

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0398

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00955

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.0357

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0425

Hom.:

197

Bravo

AF:

0.0657

Asia WGS

AF:

0.0160

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

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.54

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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