NM_001017995.3:c.*4035G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017995.3(SH3PXD2B):​c.*4035G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 843,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: SH3PXD2B NM_001017995.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.*4035G>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2	c.*4035G>T		3_prime_UTR_variant	Exon 14 of 14		XP_016864840.1
SH3PXD2B	NM_001308175.2	c.1189-8954G>T		intron_variant	Intron 12 of 12		NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.*4035G>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001017995.3	ENSP00000309714.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000830 AC: 7 AN: 843756 Hom.: 0 Cov.: 32 AF XY: 0.00000769 AC XY: 3 AN XY: 389914

African (AFR) AF: 0.0000632 AC: 1 AN: 15828

American (AMR) AF: 0.00 AC: 0 AN: 1438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5344

East Asian (EAS) AF: 0.00 AC: 0 AN: 3704

South Asian (SAS) AF: 0.00 AC: 0 AN: 16990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1652

European-Non Finnish (NFE) AF: 0.00000779 AC: 6 AN: 770124

Other (OTH) AF: 0.00 AC: 0 AN: 28004

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.51
DANN	Benign	0.54
PhyloP100		-1.6

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;