5-148927003-C-G

Variant names:

• chr5-148927003-C-G
• rs12189287
• ENST00000504690.5:n.*226-2825G>C

Variant summary

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

The ENST00000504690.5(SH3TC2):​n.*226-2825G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,110 control chromosomes in the GnomAD database, including 5,401 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 0.25 (5401 hom., cov: 32)
• Consequence: SH3TC2 ENST00000504690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 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.*226-2825G>C		intron_variant	Intron 18 of 19	5		ENSP00000425627.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38354 AN: 151992 Hom.: 5401 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.252 AC: 38365 AN: 152110 Hom.: 5401 Cov.: 32 AF XY: 0.253 AC XY: 18819 AN XY: 74352

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.293

Alfa AF: 0.151 Hom.: 314

Bravo AF: 0.240

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.8
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12189287; hg19: chr5-148306566;