rs534091900

Variant names:

• chr5-172339475-GCCGCTC-G
• rs534091900
• NM_001017995.3:c.1624_1629delGAGCGG

Your query was ambiguous. Multiple possible variants found:

• chr5-172339475-GCCGCTC-G
• chr5-172339475-GCCGCTC-GCCGCTCCCGCTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001017995.3(SH3PXD2B):​c.1624_1629delGAGCGG​(p.Glu542_Arg543del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000946 in 1,613,808 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: SH3PXD2B NM_001017995.3 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-172339475-GCCGCTC-G is Benign according to our data. Variant chr5-172339475-GCCGCTC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284621.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 = 0.00509 (776/152308) while in subpopulation AFR AF = 0.0176 (730/41566). AF 95% confidence interval is 0.0165. There are 5 homozygotes in GnomAd4. There are 353 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.1624_1629delGAGCGG	p.Glu542_Arg543del	conservative_inframe_deletion	Exon 13 of 13	NP_001017995.1
	SH3PXD2B	NM_001308175.2		c.1188+6655_1188+6660delGAGCGG		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.1624_1629delGAGCGG	p.Glu542_Arg543del	conservative_inframe_deletion	Exon 13 of 13	ENSP00000309714.5
	SH3PXD2B	ENST00000519643.5	TSL:1	c.1188+6655_1188+6660delGAGCGG		intron	N/A	ENSP00000430890.1
	SH3PXD2B	ENST00000636523.1	TSL:5	c.1227+6655_1227+6660delGAGCGG		intron	N/A	ENSP00000490082.1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152190 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00130 AC: 327 AN: 250982 AF XY: 0.000921

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000514 AC: 751 AN: 1461500 Hom.: 3 AF XY: 0.000411 AC XY: 299 AN XY: 727008

African (AFR) AF: 0.0162 AC: 542 AN: 33474

American (AMR) AF: 0.00125 AC: 56 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1111822

Other (OTH) AF: 0.00108 AC: 65 AN: 60386

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152308 Hom.: 5 Cov.: 33 AF XY: 0.00474 AC XY: 353 AN XY: 74478

African (AFR) AF: 0.0176 AC: 730 AN: 41566

American (AMR) AF: 0.00229 AC: 35 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00586

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=178/22	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs534091900; hg19: chr5-171766479;