rs1025476

Positions:

• chr5-149010200-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024577.4(SH3TC2):​c.3327+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,610,164 control chromosomes in the GnomAD database, including 129,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12796 hom., cov: 32)
  • Exomes 𝑓: 0.40 (116928 hom.)
• Consequence: SH3TC2 NM_024577.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 5-149010200-G-A is Benign according to our data. Variant chr5-149010200-G-A is described in ClinVar as [Benign]. Clinvar id is 673389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3TC2	NM_024577.4	c.3327+70C>T		intron_variant		ENST00000515425.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3TC2	ENST00000515425.6	c.3327+70C>T		intron_variant		1	NM_024577.4	P2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61787 AN: 151906 Hom.: 12790 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.398 AC: 579652 AN: 1458140 Hom.: 116928 AF XY: 0.400 AC XY: 290405 AN XY: 725492

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.407 AC: 61825 AN: 152024 Hom.: 12796 Cov.: 32 AF XY: 0.411 AC XY: 30567 AN XY: 74306

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.399

Alfa AF: 0.397 Hom.: 20153

Bravo AF: 0.392

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0050
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs1025476; hg19: chr5-148389763; COSMIC: COSV60464084; COSMIC: COSV60464084;