rs397514613
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_139242.4(MTFMT):c.382C>T(p.Arg128Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000992 in 1,613,660 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
MTFMT
NM_139242.4 stop_gained
NM_139242.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 4.09
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
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Variant 15-65026868-G-A is Pathogenic according to our data. Variant chr15-65026868-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 39828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTFMT | NM_139242.4 | c.382C>T | p.Arg128Ter | stop_gained | 2/9 | ENST00000220058.9 | |
MTFMT | XM_005254158.6 | c.535C>T | p.Arg179Ter | stop_gained | 2/9 | ||
MTFMT | XR_001751081.2 | n.561C>T | non_coding_transcript_exon_variant | 2/5 | |||
MTFMT | XR_007064421.1 | n.561C>T | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTFMT | ENST00000220058.9 | c.382C>T | p.Arg128Ter | stop_gained | 2/9 | 1 | NM_139242.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249214Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135196
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461626Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727076
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation defect type 15 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 07, 2011 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change creates a premature translational stop signal (p.Arg128*) in the MTFMT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTFMT are known to be pathogenic (PMID: 21907147, 24461907). This variant is present in population databases (rs397514613, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with combined oxidative phosphorylation deficiency (PMID: 21907147). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 39828). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Combined oxidative phosphorylation defect type 15;C4748826:Mitochondrial complex 1 deficiency, nuclear type 27 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2022 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at