5-172334334-C-T

Variant names:

• chr5-172334334-C-T
• rs17074644
• NM_001017995.3:c.*4035G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001017995.3(SH3PXD2B):​c.*4035G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 995,992 control chromosomes in the GnomAD database, including 4,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (864 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3786 hom.)
• Consequence: SH3PXD2B NM_001017995.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63
• Publications: 6 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), Orphanet, G2P, PanelApp Australia, Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-172334334-C-T is Benign according to our data. Variant chr5-172334334-C-T is described in ClinVar as Benign. ClinVar VariationId is 352738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	NM_001017995.3	MANE Select	c.*4035G>A		3_prime_UTR	Exon 13 of 13	NP_001017995.1	A1X283
	SH3PXD2B	NM_001308175.2		c.1189-8954G>A		intron	N/A	NP_001295104.1	G3V144

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	ENST00000311601.6	TSL:1 MANE Select	c.*4035G>A		3_prime_UTR	Exon 13 of 13	ENSP00000309714.5	A1X283
	SH3PXD2B	ENST00000519643.5	TSL:1	c.1189-8954G>A		intron	N/A	ENSP00000430890.1	G3V144
	SH3PXD2B	ENST00000918640.1		c.*4035G>A		3_prime_UTR	Exon 14 of 14	ENSP00000588699.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15945 AN: 152134 Hom.: 860 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.0932

GnomAD4 exome AF: 0.0940 AC: 79293 AN: 843740 Hom.: 3786 Cov.: 32 AF XY: 0.0942 AC XY: 36725 AN XY: 389910

African (AFR) AF: 0.126 AC: 1988 AN: 15828

American (AMR) AF: 0.0605 AC: 87 AN: 1438

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 535 AN: 5344

East Asian (EAS) AF: 0.115 AC: 427 AN: 3704

South Asian (SAS) AF: 0.0896 AC: 1522 AN: 16990

European-Finnish (FIN) AF: 0.0938 AC: 63 AN: 672

Middle Eastern (MID) AF: 0.104 AC: 172 AN: 1652

European-Non Finnish (NFE) AF: 0.0932 AC: 71741 AN: 770108

Other (OTH) AF: 0.0985 AC: 2758 AN: 28004

GnomAD4 genome AF: 0.105 AC: 15980 AN: 152252 Hom.: 864 Cov.: 32 AF XY: 0.104 AC XY: 7749 AN XY: 74452

African (AFR) AF: 0.128 AC: 5328 AN: 41552

American (AMR) AF: 0.0755 AC: 1155 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.119 AC: 613 AN: 5168

South Asian (SAS) AF: 0.0918 AC: 443 AN: 4828

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0990 AC: 6735 AN: 68018

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.101 Hom.: 293

Bravo AF: 0.102

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Frank-Ter Haar syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.72
DANN	Benign	0.53
PhyloP100		-1.6
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: rs17074644; hg19: chr5-171761338; COSMIC: COSV61125626; COSMIC: COSV61125626;