chr5-148927003-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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), Ambry Genetics, Orphanet
• susceptibility to mononeuropathy of the median nerve, mild

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC2	ENST00000504690.5	TSL:5	n.*226-2825G>C		intron	N/A	ENSP00000425627.1	E9PDF1

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

African (AFR) AF: 0.158 AC: 6562 AN: 41500

American (AMR) AF: 0.245 AC: 3742 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1354 AN: 3464

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5182

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3222 AN: 10568

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20852 AN: 67970

Other (OTH) AF: 0.293 AC: 621 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.8
DANN	Benign	0.70
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs12189287; hg19: chr5-148306566;