5-172347268-C-T

Variant names:

• chr5-172347268-C-T
• rs111572530
• NM_001017995.3:c.1062+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001017995.3(SH3PXD2B):​c.1062+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,613,954 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (43 hom.)
• Consequence: SH3PXD2B NM_001017995.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.134
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Frank-Ter Haar syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-172347268-C-T is Benign according to our data. Variant chr5-172347268-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0153 (2336/152224) while in subpopulation AFR AF = 0.0481 (2000/41544). AF 95% confidence interval is 0.0464. There are 57 homozygotes in GnomAd4. There are 1093 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	NM_001017995.3	MANE Select	c.1062+15G>A		intron	N/A	NP_001017995.1
	SH3PXD2B	NM_001308175.2		c.1062+15G>A		intron	N/A	NP_001295104.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	ENST00000311601.6	TSL:1 MANE Select	c.1062+15G>A		intron	N/A	ENSP00000309714.5
	SH3PXD2B	ENST00000519643.5	TSL:1	c.1062+15G>A		intron	N/A	ENSP00000430890.1
	SH3PXD2B	ENST00000636523.1	TSL:5	c.1101+15G>A		intron	N/A	ENSP00000490082.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2335 AN: 152106 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00832

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00535 AC: 1346 AN: 251440 AF XY: 0.00464

Gnomad AFR exome AF: 0.0501

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00256

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00306 AC: 4469 AN: 1461730 Hom.: 43 Cov.: 30 AF XY: 0.00295 AC XY: 2145 AN XY: 727182

African (AFR) AF: 0.0463 AC: 1548 AN: 33470

American (AMR) AF: 0.00523 AC: 234 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.000870 AC: 75 AN: 86254

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53412

Middle Eastern (MID) AF: 0.0147 AC: 85 AN: 5764

European-Non Finnish (NFE) AF: 0.00199 AC: 2211 AN: 1111894

Other (OTH) AF: 0.00470 AC: 284 AN: 60384

GnomAD4 genome AF: 0.0153 AC: 2336 AN: 152224 Hom.: 57 Cov.: 32 AF XY: 0.0147 AC XY: 1093 AN XY: 74424

African (AFR) AF: 0.0481 AC: 2000 AN: 41544

American (AMR) AF: 0.00831 AC: 127 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00241 AC: 164 AN: 68004

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00443 Hom.: 2

Bravo AF: 0.0170

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Apr 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 06, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frank-Ter Haar syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.47
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111572530; hg19: chr5-171774272;