12-57782806-C-T
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005726.6(TSFM):c.5C>T(p.Ser2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,591,124 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S2S) has been classified as Likely benign.
Frequency
Consequence
NM_005726.6 missense
Scores
Clinical Significance
Conservation
Publications
- fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSFM | NM_005726.6 | c.5C>T | p.Ser2Leu | missense_variant | Exon 1 of 6 | ENST00000652027.2 | NP_005717.3 | |
TSFM | NM_001172696.2 | c.5C>T | p.Ser2Leu | missense_variant | Exon 1 of 7 | NP_001166167.1 | ||
TSFM | NM_001172697.2 | c.5C>T | p.Ser2Leu | missense_variant | Exon 1 of 6 | NP_001166168.1 | ||
TSFM | NM_001172695.2 | c.5C>T | p.Ser2Leu | missense_variant | Exon 1 of 5 | NP_001166166.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00637 AC: 970AN: 152194Hom.: 11 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00158 AC: 339AN: 214724 AF XY: 0.00115 show subpopulations
GnomAD4 exome AF: 0.000717 AC: 1032AN: 1438812Hom.: 10 Cov.: 30 AF XY: 0.000601 AC XY: 429AN XY: 713520 show subpopulations
GnomAD4 genome AF: 0.00638 AC: 971AN: 152312Hom.: 11 Cov.: 32 AF XY: 0.00630 AC XY: 469AN XY: 74494 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:3
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Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 Benign:2
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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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at