ENST00000504690.5:n.*13-19776T>C

Variant names:

• chr5-148974661-A-G
• rs10038913
• ENST00000504690.5:n.*13-19776T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504690.5(SH3TC2):​n.*13-19776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,124 control chromosomes in the GnomAD database, including 44,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44989 hom., cov: 32)
• Consequence: SH3TC2 ENST00000504690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive hereditary demyelinating motor and sensory neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 4C

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• susceptibility to mononeuropathy of the median nerve, mild

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504690.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC2	ENST00000504690.5	TSL:5	n.*13-19776T>C		intron	N/A	ENSP00000425627.1
	SH3TC2	ENST00000510350.1	TSL:3	n.232-19776T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116104 AN: 152006 Hom.: 44966 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.764 AC: 116179 AN: 152124 Hom.: 44989 Cov.: 32 AF XY: 0.766 AC XY: 56962 AN XY: 74372

African (AFR) AF: 0.652 AC: 27042 AN: 41492

American (AMR) AF: 0.838 AC: 12816 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2642 AN: 3468

East Asian (EAS) AF: 0.974 AC: 5033 AN: 5170

South Asian (SAS) AF: 0.764 AC: 3673 AN: 4808

European-Finnish (FIN) AF: 0.810 AC: 8578 AN: 10594

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53858 AN: 67990

Other (OTH) AF: 0.761 AC: 1604 AN: 2108

Alfa AF: 0.783 Hom.: 8155

Bravo AF: 0.766

Asia WGS AF: 0.840 AC: 2917 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs10038913; hg19: chr5-148354224; COSMIC: COSV72555087;