chr12-57782806-C-T
Variant summary
Our verdict is Benign. Variant got -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. 14/19 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
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSFM | NM_005726.6 | c.5C>T | p.Ser2Leu | missense_variant | 1/6 | ENST00000652027.2 | |
TSFM | NM_001172696.2 | c.5C>T | p.Ser2Leu | missense_variant | 1/7 | ||
TSFM | NM_001172697.2 | c.5C>T | p.Ser2Leu | missense_variant | 1/6 | ||
TSFM | NM_001172695.2 | c.5C>T | p.Ser2Leu | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSFM | ENST00000652027.2 | c.5C>T | p.Ser2Leu | missense_variant | 1/6 | NM_005726.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00637 AC: 970AN: 152194Hom.: 11 Cov.: 32
GnomAD3 exomes AF: 0.00158 AC: 339AN: 214724Hom.: 2 AF XY: 0.00115 AC XY: 133AN XY: 115756
GnomAD4 exome AF: 0.000717 AC: 1032AN: 1438812Hom.: 10 Cov.: 30 AF XY: 0.000601 AC XY: 429AN XY: 713520
GnomAD4 genome ? AF: 0.00638 AC: 971AN: 152312Hom.: 11 Cov.: 32 AF XY: 0.00630 AC XY: 469AN XY: 74494
ClinVar
Submissions by phenotype
Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 02, 2020 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at