5-149047903-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024577.4(SH3TC2):c.238G>A(p.Ala80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,614,182 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A80E) has been classified as Uncertain significance.
Frequency
Consequence
NM_024577.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3TC2 | NM_024577.4 | c.238G>A | p.Ala80Thr | missense_variant | Exon 3 of 17 | ENST00000515425.6 | NP_078853.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00270 AC: 411AN: 152206Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000672 AC: 169AN: 251412Hom.: 1 AF XY: 0.000530 AC XY: 72AN XY: 135878
GnomAD4 exome AF: 0.000270 AC: 395AN: 1461858Hom.: 2 Cov.: 30 AF XY: 0.000230 AC XY: 167AN XY: 727226
GnomAD4 genome AF: 0.00271 AC: 413AN: 152324Hom.: 1 Cov.: 32 AF XY: 0.00268 AC XY: 200AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:4
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not specified Benign:1
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Charcot-Marie-Tooth disease Benign:1
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Charcot-Marie-Tooth disease type 4C Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Inborn genetic diseases Benign:1
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. -
Susceptibility to mononeuropathy of the median nerve, mild Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at