NM_001017995.3:c.105C>T

Variant names:

• chr5-172422467-G-A
• rs17074773
• NM_001017995.3:c.105C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001017995.3(SH3PXD2B):​c.105C>T​(p.Ser35Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,610,500 control chromosomes in the GnomAD database, including 82,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7494 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74940 hom.)
• Consequence: SH3PXD2B NM_001017995.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.18
• Publications: 20 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-172422467-G-A is Benign according to our data. Variant chr5-172422467-G-A is described in ClinVar as Benign. ClinVar VariationId is 257056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.105C>T	p.Ser35Ser	synonymous_variant	Exon 2 of 13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	NM_001308175.2	c.105C>T	p.Ser35Ser	synonymous_variant	Exon 2 of 13		NP_001295104.1
SH3PXD2B	XM_017009351.2	c.105C>T	p.Ser35Ser	synonymous_variant	Exon 2 of 14		XP_016864840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.105C>T	p.Ser35Ser	synonymous_variant	Exon 2 of 13	1	NM_001017995.3	ENSP00000309714.5
SH3PXD2B	ENST00000519643.5	c.105C>T	p.Ser35Ser	synonymous_variant	Exon 2 of 13	1		ENSP00000430890.1
SH3PXD2B	ENST00000636523.1	c.60C>T	p.Ser20Ser	synonymous_variant	Exon 2 of 14	5		ENSP00000490082.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45702 AN: 151786 Hom.: 7481 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.351 AC: 86604 AN: 246870 AF XY: 0.345

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.312 AC: 454464 AN: 1458596 Hom.: 74940 Cov.: 40 AF XY: 0.313 AC XY: 226690 AN XY: 725382

African (AFR) AF: 0.247 AC: 8247 AN: 33454

American (AMR) AF: 0.483 AC: 21437 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7303 AN: 26088

East Asian (EAS) AF: 0.629 AC: 24935 AN: 39666

South Asian (SAS) AF: 0.382 AC: 32759 AN: 85716

European-Finnish (FIN) AF: 0.282 AC: 14790 AN: 52528

Middle Eastern (MID) AF: 0.273 AC: 1575 AN: 5762

European-Non Finnish (NFE) AF: 0.292 AC: 323873 AN: 1110688

Other (OTH) AF: 0.324 AC: 19545 AN: 60294

GnomAD4 genome AF: 0.301 AC: 45745 AN: 151904 Hom.: 7494 Cov.: 32 AF XY: 0.307 AC XY: 22757 AN XY: 74230

African (AFR) AF: 0.243 AC: 10055 AN: 41434

American (AMR) AF: 0.387 AC: 5897 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.669 AC: 3452 AN: 5160

South Asian (SAS) AF: 0.380 AC: 1817 AN: 4780

European-Finnish (FIN) AF: 0.269 AC: 2839 AN: 10556

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19815 AN: 67944

Other (OTH) AF: 0.296 AC: 625 AN: 2114

Alfa AF: 0.294 Hom.: 20050

Bravo AF: 0.307

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Frank-Ter Haar syndrome Benign:2

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.92
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs17074773; hg19: chr5-171849471; COSMIC: COSV61128225;