rs146666910
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_024577.4(SH3TC2):c.1443C>T(p.Asp481=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000566 in 1,613,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 1 hom. )
Consequence
SH3TC2
NM_024577.4 synonymous
NM_024577.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.49
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 5-149028289-G-A is Benign according to our data. Variant chr5-149028289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 215534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-149028289-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.49 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3TC2 | NM_024577.4 | c.1443C>T | p.Asp481= | synonymous_variant | 11/17 | ENST00000515425.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3TC2 | ENST00000515425.6 | c.1443C>T | p.Asp481= | synonymous_variant | 11/17 | 1 | NM_024577.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000434 AC: 109AN: 251132Hom.: 1 AF XY: 0.000508 AC XY: 69AN XY: 135744
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GnomAD4 exome AF: 0.000592 AC: 865AN: 1461630Hom.: 1 Cov.: 80 AF XY: 0.000605 AC XY: 440AN XY: 727094
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GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 23, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 09, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | SH3TC2: BP4, BS1 - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at