NM_000255.4:c.878A>G
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 3P and 8B. PM1PP2BP4_StrongBS2
The NM_000255.4(MMUT):c.878A>G(p.Gln293Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000526 in 1,613,754 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q293P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000255.4 missense
Scores
Clinical Significance
Conservation
Publications
- methylmalonic aciduria due to methylmalonyl-CoA mutase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- vitamin B12-unresponsive methylmalonic acidemia type mut-Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- vitamin B12-unresponsive methylmalonic acidemia type mut0Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MMUT | NM_000255.4 | c.878A>G | p.Gln293Arg | missense_variant | Exon 4 of 13 | ENST00000274813.4 | NP_000246.2 | |
MMUT | XM_005249143.4 | c.878A>G | p.Gln293Arg | missense_variant | Exon 4 of 13 | XP_005249200.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152224Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000322 AC: 81AN: 251342 AF XY: 0.000265 show subpopulations
GnomAD4 exome AF: 0.000541 AC: 790AN: 1461412Hom.: 2 Cov.: 31 AF XY: 0.000519 AC XY: 377AN XY: 727022 show subpopulations
GnomAD4 genome AF: 0.000387 AC: 59AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74510 show subpopulations
ClinVar
Submissions by phenotype
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency Uncertain:4
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not provided Uncertain:2Benign:1
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not specified Uncertain:1
The c.878A>G (p.Q293R) alteration is located in exon 4 (coding exon 3) of the MUT gene. This alteration results from a A to G substitution at nucleotide position 878, causing the glutamine (Q) at amino acid position 293 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency Uncertain:1
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MMUT-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at