chr11-86556669-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000393324.7(ME3):c.351C>A(p.Asn117Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
ME3
ENST00000393324.7 missense
ENST00000393324.7 missense
Scores
6
5
7
Clinical Significance
Conservation
PhyloP100: -2.08
Genes affected
ME3 (HGNC:6985): (malic enzyme 3) Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.898
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ME3 | NM_001161586.3 | c.351C>A | p.Asn117Lys | missense_variant | 4/15 | ENST00000543262.6 | |
ME3 | NR_172888.1 | n.658C>A | non_coding_transcript_exon_variant | 4/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ME3 | ENST00000543262.6 | c.351C>A | p.Asn117Lys | missense_variant | 4/15 | 1 | NM_001161586.3 | P1 | |
ENST00000524610.1 | n.269-66056G>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251234Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135746
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461820Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727222
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74344
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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 | Nov 02, 2021 | The c.351C>A (p.N117K) alteration is located in exon 4 (coding exon 3) of the ME3 gene. This alteration results from a C to A substitution at nucleotide position 351, causing the asparagine (N) at amino acid position 117 to be replaced by a lysine (K). 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
Uncertain
DEOGEN2
Uncertain
D;D;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Uncertain
D;D;.;D;.
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of methylation at N117 (P = 0.014);Gain of methylation at N117 (P = 0.014);Gain of methylation at N117 (P = 0.014);.;Gain of methylation at N117 (P = 0.014);
MVP
MPC
1.5
ClinPred
D
GERP RS
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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