chr5-172334380-C-T

Position:

chr5-172334380-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001017995.3(SH3PXD2B):c.*3989G>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 0.000468 in 992,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SH3PXD2B
NM_001017995.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.295

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-172334380-C-T is Benign according to our data. Variant chr5-172334380-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 905555.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00198 (302/152354) while in subpopulation AFR AF= 0.00676 (281/41584). AF 95% confidence interval is 0.00611. There are 1 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SH3PXD2B	NM_001017995.3 linkuse as main transcript	c.*3989G>A	3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2 linkuse as main transcript	c.*3989G>A	3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2 linkuse as main transcript	c.1189-9000G>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.*3989G>A	3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1
SH3PXD2B	ENST00000519643.5 linkuse as main transcript	c.1189-9000G>A	intron_variant		1		ENSP00000430890
SH3PXD2B	ENST00000518522.5 linkuse as main transcript	c.201-611G>A	intron_variant		5		ENSP00000428076
SH3PXD2B	ENST00000636523.1 linkuse as main transcript	c.1229-9000G>A	intron_variant		5		ENSP00000490082

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

302

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.000194

AC:

163

AN:

840262

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

388252

show subpopulations

Gnomad4 AFR exome

AF:

0.00948

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000467

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152354

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00676

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000933

Hom.:

Bravo

AF:

0.00221

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Frank-Ter Haar syndrome

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.7

DANN

Benign

0.83

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