chr12-57793041-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005726.6(TSFM):āc.539G>Cā(p.Gly180Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G180G) has been classified as Likely benign.
Frequency
Consequence
NM_005726.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSFM | NM_005726.6 | c.539G>C | p.Gly180Ala | missense_variant | 5/6 | ENST00000652027.2 | |
TSFM | NM_001172696.2 | c.602G>C | p.Gly201Ala | missense_variant | 6/7 | ||
TSFM | NM_001172697.2 | c.539G>C | p.Gly180Ala | missense_variant | 5/6 | ||
TSFM | NM_001172695.2 | c.484-3136G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSFM | ENST00000652027.2 | c.539G>C | p.Gly180Ala | missense_variant | 5/6 | NM_005726.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000552 AC: 84AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000151 AC: 38AN: 251064Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135704
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461394Hom.: 1 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 726998
GnomAD4 genome AF: 0.000551 AC: 84AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 25, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 19, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at