rs55853803

Variant names:

Variant summary

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

The NM_024577.4(SH3TC2):c.3472G>A(p.Val1158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,614,142 control chromosomes in the GnomAD database, including 920 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 56 hom., cov: 32)

Exomes 𝑓: 0.033 ( 864 hom. )

Consequence

SH3TC2
NM_024577.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

SH3TC2 (HGNC:29427): (SH3 domain and tetratricopeptide repeats 2) This gene encodes a protein with two N-terminal Src homology 3 (SH3) domains and 10 tetratricopeptide repeat (TPR) motifs, and is a member of a small gene family. The gene product has been proposed to be an adapter or docking molecule. Mutations in this gene result in autosomal recessive Charcot-Marie-Tooth disease type 4C, a childhood-onset neurodegenerative disease characterized by demyelination of motor and sensory neurons. [provided by RefSeq, Jul 2008]

SH3TC2 links:

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 (MetaRNN=0.002704382).

BP6

Variant 5-149008857-C-T is Benign according to our data. Variant chr5-149008857-C-T is described in ClinVar as [Benign]. Clinvar id is 221185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-149008857-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0221 (3362/152342) while in subpopulation SAS AF= 0.043 (208/4832). AF 95% confidence interval is 0.0383. There are 56 homozygotes in gnomad4. There are 1649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3TC2	NM_024577.4 link	c.3472G>A	p.Val1158Ile	missense_variant	Exon 15 of 17	ENST00000515425.6	NP_078853.2	Q8TF17-1A0A514TP98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000515425.6 link	c.3472G>A	p.Val1158Ile	missense_variant	Exon 15 of 17	1	NM_024577.4	ENSP00000423660.1		Q8TF17-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3361

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00540

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0606

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0428

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0272

AC:

6842

AN:

251490

Hom.:

139

AF XY:

0.0290

AC XY:

3941

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00554

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0575

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0309

Gnomad OTH exome

AF:

0.0287

GnomAD4 exome

AF:

0.0326

AC:

47678

AN:

1461800

Hom.:

864

Cov.:

AF XY:

0.0330

AC XY:

24010

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0582

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0457

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0318

GnomAD4 genome

AF:

0.0221

AC:

3362

AN:

152342

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1649

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00539

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.0606

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0430

Gnomad4 FIN

AF:

0.0201

Gnomad4 NFE

AF:

0.0316

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0306

Hom.:

121

Bravo

AF:

0.0206

TwinsUK

AF:

0.0316

AC:

117

ALSPAC

AF:

0.0358

AC:

138

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.0336

AC:

289

ExAC

AF:

0.0271

AC:

3287

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0318

EpiControl

AF:

0.0296

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Sep 26, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 4C

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Susceptibility to mononeuropathy of the median nerve, mild

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 25, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.071

T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.098

Sift

Benign

0.25

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0020

B;.

Vest4

0.089

MPC

0.035

ClinPred

0.0029

GERP RS

1.7

Varity_R

0.026

gMVP

0.077

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over