rs575038087
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000255.4(MMUT):c.191C>T(p.Pro64Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,136 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P64P) has been classified as Likely benign.
Frequency
Consequence
NM_000255.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMUT | NM_000255.4 | c.191C>T | p.Pro64Leu | missense_variant | 2/13 | ENST00000274813.4 | |
MMUT | XM_005249143.4 | c.191C>T | p.Pro64Leu | missense_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMUT | ENST00000274813.4 | c.191C>T | p.Pro64Leu | missense_variant | 2/13 | 1 | NM_000255.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727242
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 64 of the MUT protein (p.Pro64Leu). This variant is present in population databases (rs575038087, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MUT-related conditions. ClinVar contains an entry for this variant (Variation ID: 523066). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 18, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at