rs879253841
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000255.4(MMUT):c.1181_1182insT(p.Leu394PhefsTer30) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L394L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000255.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMUT | NM_000255.4 | c.1181_1182insT | p.Leu394PhefsTer30 | frameshift_variant | 6/13 | ENST00000274813.4 | |
MMUT | XM_005249143.4 | c.1181_1182insT | p.Leu394PhefsTer30 | frameshift_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMUT | ENST00000274813.4 | c.1181_1182insT | p.Leu394PhefsTer30 | frameshift_variant | 6/13 | 1 | NM_000255.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727212
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 222930). This premature translational stop signal has been observed in individual(s) with methylmalonic acidemia (PMID: 26270765). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu394Phefs*30) in the MUT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). - |
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | University Children's Hospital, University of Zurich | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at