rs397514614
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_139242.4(MTFMT):c.374C>T(p.Ser125Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S125S) has been classified as Likely benign.
Frequency
Consequence
NM_139242.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTFMT | NM_139242.4 | c.374C>T | p.Ser125Leu | missense_variant | 2/9 | ENST00000220058.9 | |
MTFMT | XM_005254158.6 | c.527C>T | p.Ser176Leu | missense_variant | 2/9 | ||
MTFMT | XR_001751081.2 | n.553C>T | non_coding_transcript_exon_variant | 2/5 | |||
MTFMT | XR_007064421.1 | n.553C>T | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTFMT | ENST00000220058.9 | c.374C>T | p.Ser125Leu | missense_variant | 2/9 | 1 | NM_139242.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249212Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135186
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461646Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727094
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 15 Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | DASA | Feb 05, 2022 | The c.374C>T;p.(Ser125Leu) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar: 39829; PMID: 21907147) - PS4_supporting. The variant is present at low allele frequencies population databases (rs397514614 – gnomAD 0.00004013%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Ser125Leu) was detected in trans with a pathogenic variant (PMID: 21907147) - PM3_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | This variant has been previously reported as disease-causing and was found once in our laboratory in trans with another pathogenic variant in a 12-year-old female with mitochondrial disorder, Leigh disease, intellectual disability, short stature, microcephaly, PDA, brachydactyly, pes planus, congenital hypothyroidism - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 07, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at