Variant 5-172333542-A-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_001017995.3(SH3PXD2B):c.*4827T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 974,356 control chromosomes in the GnomAD database, including 90,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 18512 hom., cov: 28)

Exomes 𝑓: 0.51 ( 71823 hom. )

Consequence

SH3PXD2B
NM_001017995.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.504

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:

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 (BayesDel_noAF=-0.6).

BP6

Variant 5-172333542-A-T is Benign according to our data. Variant chr5-172333542-A-T is described in ClinVar as [Benign]. Clinvar id is 352727.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SH3PXD2B	NM_001017995.3 linkuse as main transcript	c.*4827T>A	3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2 linkuse as main transcript	c.*4827T>A	3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2 linkuse as main transcript	c.1189-8162T>A	intron_variant			NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6 linkuse as main transcript	c.*4827T>A		3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

73647

AN:

131230

Hom.:

18509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.755

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.606

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.564

GnomAD4 exome

AF:

0.510

AC:

430366

AN:

843070

Hom.:

71823

Cov.:

AF XY:

0.514

AC XY:

208104

AN XY:

404726

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.521

Gnomad4 ASJ exome

AF:

0.530

Gnomad4 EAS exome

AF:

0.498

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.473

Gnomad4 NFE exome

AF:

0.505

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.561

AC:

73676

AN:

131286

Hom.:

18512

Cov.:

AF XY:

0.562

AC XY:

36031

AN XY:

64082

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.631

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.755

Gnomad4 FIN

AF:

0.546

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.463

Hom.:

1006

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Frank-Ter Haar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

DANN

Benign

0.87

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