5-172333540-T-TA

Position:

• chr5-172333540-T-TA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001017995.3(SH3PXD2B):​c.*4828_*4829insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0038 (0 hom.)
• Consequence: SH3PXD2B NM_001017995.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000148 (22/148854) while in subpopulation EAS AF= 0.000393 (2/5092). AF 95% confidence interval is 0.0000805. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.*4828_*4829insT		3_prime_UTR_variant	13/13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2	c.*4828_*4829insT		3_prime_UTR_variant	14/14		XP_016864840.1
SH3PXD2B	NM_001308175.2	c.1189-8161_1189-8160insT		intron_variant			NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.*4828_*4829insT		3_prime_UTR_variant	13/13	1	NM_001017995.3	ENSP00000309714	P1

Frequencies

GnomAD3 genomes AF: 0.000148 AC: 22 AN: 148746 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00384 AC: 3355 AN: 873594 Hom.: 0 Cov.: 0 AF XY: 0.00371 AC XY: 1552 AN XY: 418794

Gnomad4 AFR exome AF: 0.00510

Gnomad4 AMR exome AF: 0.00829

Gnomad4 ASJ exome AF: 0.00454

Gnomad4 EAS exome AF: 0.00661

Gnomad4 SAS exome AF: 0.00135

Gnomad4 FIN exome AF: 0.00750

Gnomad4 NFE exome AF: 0.00383

Gnomad4 OTH exome AF: 0.00445

GnomAD4 genome AF: 0.000148 AC: 22 AN: 148854 Hom.: 0 Cov.: 0 AF XY: 0.000138 AC XY: 10 AN XY: 72508

Gnomad4 AFR AF: 0.000173

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000102

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

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: rs35951290; hg19: chr5-171760544;