Variant rs17722227 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024577.4(SH3TC2):c.1350G>A(p.Pro450Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,614,122 control chromosomes in the GnomAD database, including 2,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 296 hom., cov: 32)

Exomes 𝑓: 0.018 ( 1999 hom. )

Consequence

SH3TC2
NM_024577.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.20

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-149028382-C-T is Benign according to our data. Variant chr5-149028382-C-T is described in ClinVar as [Benign]. Clinvar id is 139101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-149028382-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC2	NM_024577.4 link	c.1350G>A	p.Pro450Pro	synonymous_variant	11/17	ENST00000515425.6	NP_078853.2	Q8TF17-1A0A514TP98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000515425.6 link	c.1350G>A	p.Pro450Pro	synonymous_variant	11/17	1	NM_024577.4	ENSP00000423660.1		Q8TF17-1

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3921

AN:

152180

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0583

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0550

AC:

13794

AN:

251022

Hom.:

1583

AF XY:

0.0471

AC XY:

6396

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.0973

Gnomad SAS exome

AF:

0.0533

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0178

AC:

26032

AN:

1461824

Hom.:

1999

Cov.:

AF XY:

0.0177

AC XY:

12858

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00499

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.00708

Gnomad4 EAS exome

AF:

0.0768

Gnomad4 SAS exome

AF:

0.0500

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00498

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0258

AC:

3932

AN:

152298

Hom.:

296

Cov.:

AF XY:

0.0296

AC XY:

2205

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.0581

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00615

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0172

Hom.:

243

Bravo

AF:

0.0373

Asia WGS

AF:

0.0970

AC:

335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 20, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 05, 2015	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease type 4C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Susceptibility to mononeuropathy of the median nerve, mild

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

DANN

Benign

0.49

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