chr18-50895906-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002396.5(ME2):āc.86T>Cā(p.Met29Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000020 ( 0 hom. )
Consequence
ME2
NM_002396.5 missense
NM_002396.5 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.51
Genes affected
ME2 (HGNC:6984): (malic enzyme 2) This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27053717).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ME2 | NM_002396.5 | c.86T>C | p.Met29Thr | missense_variant | 2/16 | ENST00000321341.11 | |
ME2 | NM_001168335.2 | c.86T>C | p.Met29Thr | missense_variant | 2/14 | ||
ME2 | NR_174094.1 | n.289T>C | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ME2 | ENST00000321341.11 | c.86T>C | p.Met29Thr | missense_variant | 2/16 | 1 | NM_002396.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251126Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135762
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GnomAD4 exome AF: 0.0000199 AC: 29AN: 1460802Hom.: 0 Cov.: 29 AF XY: 0.0000193 AC XY: 14AN XY: 726782
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | The c.86T>C (p.M29T) alteration is located in exon 2 (coding exon 1) of the ME2 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the methionine (M) at amino acid position 29 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;T;D;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;.;.
REVEL
Benign
Sift
Benign
T;.;T;.;.;.
Sift4G
Benign
T;.;T;.;.;.
Polyphen
B;.;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at M29 (P = 0.0582);Gain of phosphorylation at M29 (P = 0.0582);Gain of phosphorylation at M29 (P = 0.0582);Gain of phosphorylation at M29 (P = 0.0582);Gain of phosphorylation at M29 (P = 0.0582);Gain of phosphorylation at M29 (P = 0.0582);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at