rs765917146
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_052845.4(MMAB):āc.316A>Gā(p.Lys106Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_052845.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAB | NM_052845.4 | c.316A>G | p.Lys106Glu | missense_variant | 4/9 | ENST00000545712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAB | ENST00000545712.7 | c.316A>G | p.Lys106Glu | missense_variant | 4/9 | 1 | NM_052845.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251458Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135910
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461772Hom.: 1 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727202
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Methylmalonic aciduria, cblB type Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces lysine with glutamic acid at codon 106 of the MMAB protein (p.Lys106Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs765917146, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with MMAB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at