NM_001017995.3:c.1403G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001017995.3(SH3PXD2B):c.1403G>A(p.Arg468Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SH3PXD2B
NM_001017995.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.70

Publications

7 publications found

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]

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

SH3PXD2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039975703).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000131 (20/152360) while in subpopulation EAS AF = 0.00154 (8/5188). AF 95% confidence interval is 0.000767. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.1403G>A	p.Arg468Gln	missense	Exon 13 of 13	NP_001017995.1	A1X283
	SH3PXD2B	NM_001308175.2		c.1188+6434G>A		intron	N/A	NP_001295104.1	G3V144

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3PXD2B	ENST00000311601.6	TSL:1 MANE Select	c.1403G>A	p.Arg468Gln	missense	Exon 13 of 13	ENSP00000309714.5	A1X283
SH3PXD2B	ENST00000519643.5	TSL:1	c.1188+6434G>A		intron	N/A	ENSP00000430890.1	G3V144
SH3PXD2B	ENST00000918640.1		c.1505G>A	p.Arg502Gln	missense	Exon 14 of 14	ENSP00000588699.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000175

AC:

AN:

251280

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000145

AC:

212

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

109

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00151

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000126

AC:

140

AN:

1112000

Other (OTH)

AF:

0.0000828

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41596

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Frank-Ter Haar syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.079

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Uncertain

0.013

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.46

MVP

0.66

MPC

0.63

ClinPred

0.089

GERP RS

5.9

Varity_R

0.22

gMVP

0.41

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over