5-172333541-A-T

Position:

• chr5-172333541-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001017995.3(SH3PXD2B):​c.*4828T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (92 hom., cov: 0)
  • Exomes 𝑓: 0.060 (58 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH3PXD2B NM_001017995.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.198

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-172333541-A-T is Benign according to our data. Variant chr5-172333541-A-T is described in ClinVar as [Benign]. Clinvar id is 352726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.*4828T>A		3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2	c.*4828T>A		3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2	c.1189-8161T>A		intron_variant			NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.*4828T>A		3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 3649 AN: 24840 Hom.: 92 Cov.: 0

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0636

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.158

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0600 AC: 14536 AN: 242266 Hom.: 58 Cov.: 0 AF XY: 0.0635 AC XY: 7285 AN XY: 114642

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.0521

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0824

GnomAD4 genome AF: 0.147 AC: 3658 AN: 24858 Hom.: 92 Cov.: 0 AF XY: 0.144 AC XY: 1731 AN XY: 12006

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0636

Gnomad4 EAS AF: 0.0960

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.158

Alfa AF: 0.0430 Hom.: 5

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.82
CADD	Benign	1.5
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs1139996; hg19: chr5-171760545; COSMIC: COSV61126638;