6-49435569-T-C
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 3P and 20B. PM1PP2BP4_StrongBP6_Very_StrongBA1
The NM_000255.4(MMUT):c.2011A>G(p.Ile671Val) variant causes a missense change. The variant allele was found at a frequency of 0.606 in 1,613,526 control chromosomes in the GnomAD database, including 300,357 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.
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: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MMUT | NM_000255.4 | c.2011A>G | p.Ile671Val | missense_variant | Exon 12 of 13 | ENST00000274813.4 | NP_000246.2 | |
MMUT | XM_005249143.4 | c.2011A>G | p.Ile671Val | missense_variant | Exon 12 of 13 | XP_005249200.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.588 AC: 89383AN: 151988Hom.: 26651 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.562 AC: 140906AN: 250646 AF XY: 0.573 show subpopulations
GnomAD4 exome AF: 0.608 AC: 888933AN: 1461420Hom.: 273683 Cov.: 55 AF XY: 0.610 AC XY: 443448AN XY: 726986 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.588 AC: 89445AN: 152106Hom.: 26674 Cov.: 33 AF XY: 0.583 AC XY: 43327AN XY: 74362 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency Benign:6
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not specified Benign:5
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Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 58% of total chromosomes in ExAC -
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not provided Benign:2
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Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at