Variant chr5-172333700-AGAGT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001017995.3(SH3PXD2B):c.*4665_*4668del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000954 in 1,289,418 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 21 hom. )

Consequence

SH3PXD2B
NM_001017995.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.830

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000591 (90/152290) while in subpopulation SAS AF= 0.0172 (83/4824). AF 95% confidence interval is 0.0142. There are 2 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SH3PXD2B	NM_001017995.3 linkuse as main transcript	c.4665_4668del	3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2 linkuse as main transcript	c.4665_4668del	3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2 linkuse as main transcript	c.1189-8324_1189-8321del	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.4665_4668del		3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00231

AC:

310

AN:

134130

Hom.:

AF XY:

0.00310

AC XY:

227

AN XY:

73146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000957

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000566

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.00100

AC:

1140

AN:

1137128

Hom.:

AF XY:

0.00147

AC XY:

821

AN XY:

557816

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000354

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000779

Gnomad4 SAS exome

AF:

0.0137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000510

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000591

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000136

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Frank-Ter Haar syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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