chr5-172347268-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.134
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH3PXD2BNM_001017995.3 linkc.1062+15G>A intron_variant Intron 11 of 12 ENST00000311601.6 NP_001017995.1 A1X283
SH3PXD2BNM_001308175.2 linkc.1062+15G>A intron_variant Intron 11 of 12 NP_001295104.1 G3V144
SH3PXD2BXM_017009351.2 linkc.1146+15G>A intron_variant Intron 12 of 13 XP_016864840.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH3PXD2BENST00000311601.6 linkc.1062+15G>A intron_variant Intron 11 of 12 1 NM_001017995.3 ENSP00000309714.5 A1X283
SH3PXD2BENST00000519643.5 linkc.1062+15G>A intron_variant Intron 11 of 12 1 ENSP00000430890.1 G3V144
SH3PXD2BENST00000636523.1 linkc.1101+15G>A intron_variant Intron 12 of 13 5 ENSP00000490082.1 A0A1B0GUF2
SH3PXD2BENST00000518522.5 linkc.72+15G>A intron_variant Intron 2 of 3 5 ENSP00000428076.1 H0YAU1

Frequencies

GnomAD3 genomes
AF:
0.0154
AC:
2335
AN:
152106
Hom.:
57
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00535
AC:
1346
AN:
251440
Hom.:
23
AF XY:
0.00464
AC XY:
630
AN XY:
135900
show subpopulations
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 SAS exome
AF:
0.000915
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0463
Gnomad4 AMR exome
AF:
0.00523
Gnomad4 ASJ exome
AF:
0.000344
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.000870
Gnomad4 FIN exome
AF:
0.000374
Gnomad4 NFE exome
AF:
0.00199
Gnomad4 OTH exome
AF:
0.00470
GnomAD4 genome
AF:
0.0153
AC:
2336
AN:
152224
Hom.:
57
Cov.:
32
AF XY:
0.0147
AC XY:
1093
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0481
Gnomad4 AMR
AF:
0.00831
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00241
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00140
Hom.:
0
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
LINK: link

Submissions by phenotype

not provided Benign:4
-
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

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

- -

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 v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
7.2
DANN
Benign
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111572530; hg19: chr5-171774272; API