5-148933204-T-C

Variant names:

• chr5-148933204-T-C
• rs7729953
• ENST00000504690.5:n.*226-9026A>G

Variant summary

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

The ENST00000504690.5(SH3TC2):​n.*226-9026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,112 control chromosomes in the GnomAD database, including 8,986 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 0.32 (8986 hom., cov: 32)
• Consequence: SH3TC2 ENST00000504690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000504690.5	n.*226-9026A>G		intron_variant	Intron 18 of 19	5		ENSP00000425627.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49328 AN: 151994 Hom.: 8986 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.324 AC: 49349 AN: 152112 Hom.: 8986 Cov.: 32 AF XY: 0.326 AC XY: 24234 AN XY: 74378

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.345

Alfa AF: 0.383 Hom.: 15997

Bravo AF: 0.302

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7729953; hg19: chr5-148312767;