NM_139242.4:c.1100_1101delTT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_139242.4(MTFMT):c.1100_1101delTT(p.Phe367SerfsTer22) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000131 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_139242.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTFMT | ENST00000220058.9 | c.1100_1101delTT | p.Phe367SerfsTer22 | frameshift_variant | Exon 9 of 9 | 1 | NM_139242.4 | ENSP00000220058.4 | ||
MTFMT | ENST00000558460.5 | n.1100_1101delTT | non_coding_transcript_exon_variant | Exon 9 of 10 | 5 | ENSP00000452646.1 | ||||
MTFMT | ENST00000560717.5 | n.*570_*571delTT | non_coding_transcript_exon_variant | Exon 8 of 8 | 5 | ENSP00000457257.1 | ||||
MTFMT | ENST00000560717.5 | n.*570_*571delTT | 3_prime_UTR_variant | Exon 8 of 8 | 5 | ENSP00000457257.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248660Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134914
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Mitochondrial oxidative phosphorylation disorder Pathogenic:1
The p.Phe367SerfsX22 (NM_139242.3 c.1100_1101delTT) variant in MTFMT has been pr eviously reported in 1 compound heterozygous individual with combined oxidative phosphorylation deficiency and mitochondrial disorders (Taylor 2014). This vari ant has been identified in (2/126,516) of European chromosomes by the Genome Agg regation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs754222633). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 367 and leads to a premature termination codon 22 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Biallelic loss of function of the MTFMT gene has been associated wi th combined oxidative phosphorylation deficiency and mitochondrial disorders. In summary, the p.Phe367SerfsX22 variant is pathogenic for combined oxidative phos phorylation deficiency in an autosomal recessive manner based on a predicted var iant effect, biallelic occurrence in an individual with this disease and very lo w population frequency. -
not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at