chr11-86508838-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000393324.7(ME3):c.497G>A(p.Gly166Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
ME3
ENST00000393324.7 missense
ENST00000393324.7 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 5.23
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ME3 | NM_001161586.3 | c.497G>A | p.Gly166Asp | missense_variant | 5/15 | ENST00000543262.6 | |
ME3 | NR_172888.1 | n.804G>A | non_coding_transcript_exon_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ME3 | ENST00000543262.6 | c.497G>A | p.Gly166Asp | missense_variant | 5/15 | 1 | NM_001161586.3 | P1 | |
ENST00000524610.1 | n.268+76196C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461408Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727044
GnomAD4 exome
AF:
AC:
17
AN:
1461408
Hom.:
Cov.:
30
AF XY:
AC XY:
8
AN XY:
727044
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
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 | Dec 07, 2021 | The c.497G>A (p.G166D) alteration is located in exon 5 (coding exon 4) of the ME3 gene. This alteration results from a G to A substitution at nucleotide position 497, causing the glycine (G) at amino acid position 166 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;.;T
Polyphen
B;B;.;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);Gain of solvent accessibility (P = 0.0648);.;
MVP
MPC
0.86
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at