chr6-83398435-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002395.6(ME1):c.294G>A(p.Met98Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,602,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ME1
NM_002395.6 missense
NM_002395.6 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 7.90
Genes affected
ME1 (HGNC:6983): (malic enzyme 1) This gene encodes a cytosolic, NADP-dependent enzyme that generates NADPH for fatty acid biosynthesis. The activity of this enzyme, the reversible oxidative decarboxylation of malate, links the glycolytic and citric acid cycles. The regulation of expression for this gene is complex. Increased expression can result from elevated levels of thyroid hormones or by higher proportions of carbohydrates in the diet. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ME1 | NM_002395.6 | c.294G>A | p.Met98Ile | missense_variant | 3/14 | ENST00000369705.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ME1 | ENST00000369705.4 | c.294G>A | p.Met98Ile | missense_variant | 3/14 | 1 | NM_002395.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000369 AC: 9AN: 243942Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 131936
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GnomAD4 exome AF: 0.0000145 AC: 21AN: 1450628Hom.: 0 Cov.: 28 AF XY: 0.00000693 AC XY: 5AN XY: 721768
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74304
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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 | Oct 03, 2022 | The c.294G>A (p.M98I) alteration is located in exon 3 (coding exon 3) of the ME1 gene. This alteration results from a G to A substitution at nucleotide position 294, causing the methionine (M) at amino acid position 98 to be replaced by an isoleucine (I). 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
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of phosphorylation at T103 (P = 0.0953);
MVP
MPC
ClinPred
D
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