Variant 5-172334334-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_001017995.3(SH3PXD2B):c.*4035G>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 0.0957 in 995,992 control chromosomes in the GnomAD database, including 4,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 864 hom., cov: 32)

Exomes 𝑓: 0.094 ( 3786 hom. )

Consequence

SH3PXD2B
NM_001017995.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

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=-0.81).

BP6

Variant 5-172334334-C-T is Benign according to our data. Variant chr5-172334334-C-T is described in ClinVar as [Benign]. Clinvar id is 352738.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SH3PXD2B	NM_001017995.3 linkuse as main transcript	c.*4035G>A	3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2 linkuse as main transcript	c.*4035G>A	3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2 linkuse as main transcript	c.1189-8954G>A	intron_variant			NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SH3PXD2B	ENST00000311601.6 linkuse as main transcript	c.*4035G>A	3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1
SH3PXD2B	ENST00000519643.5 linkuse as main transcript	c.1189-8954G>A	intron_variant		1		ENSP00000430890
SH3PXD2B	ENST00000518522.5 linkuse as main transcript	c.201-565G>A	intron_variant		5		ENSP00000428076
SH3PXD2B	ENST00000636523.1 linkuse as main transcript	c.1229-8954G>A	intron_variant		5		ENSP00000490082

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15945

AN:

152134

Hom.:

860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0917

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.0932

GnomAD4 exome

AF:

0.0940

AC:

79293

AN:

843740

Hom.:

3786

Cov.:

AF XY:

0.0942

AC XY:

36725

AN XY:

389910

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0605

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.0896

Gnomad4 FIN exome

AF:

0.0938

Gnomad4 NFE exome

AF:

0.0932

Gnomad4 OTH exome

AF:

0.0985

GnomAD4 genome

AF:

0.105

AC:

15980

AN:

152252

Hom.:

864

Cov.:

AF XY:

0.104

AC XY:

7749

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0918

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.101

Hom.:

177

Bravo

AF:

0.102

Asia WGS

AF:

0.109

AC:

379

AN:

3478

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 13, 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

-0.81

CADD

Benign

0.72

DANN

Benign

0.53

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