5-148974661-A-G

Position:

• chr5-148974661-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504690.5(SH3TC2):​c.*13-19776T>C variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3TC2	ENST00000504690.5	c.*13-19776T>C		intron_variant, NMD_transcript_variant		5
SH3TC2	ENST00000510350.1	n.232-19776T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.761

Alfa AF: 0.786 Hom.: 7973

Bravo AF: 0.766

Asia WGS AF: 0.840 AC: 2917 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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