5-148933204-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• susceptibility to mononeuropathy of the median nerve, mild

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

ACMG classification

Our verdict: Benign. The variant received -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.

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.*226-9026A>G		intron	N/A	ENSP00000425627.1	E9PDF1

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

African (AFR) AF: 0.198 AC: 8219 AN: 41514

American (AMR) AF: 0.274 AC: 4190 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3472

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5178

South Asian (SAS) AF: 0.432 AC: 2076 AN: 4808

European-Finnish (FIN) AF: 0.438 AC: 4632 AN: 10580

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.404 AC: 27487 AN: 67956

Other (OTH) AF: 0.345 AC: 730 AN: 2114

Alfa AF: 0.363 Hom.: 24218

Bravo AF: 0.302

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.68
PhyloP100		-0.79

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7729953;

hg19: chr5-148312767;