Variant 11-86448228-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006680.3(ME3):c.1159G>A(p.Glu387Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ME3
NM_006680.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Variant links:

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]

ME3 links:

ME3 (HGNC:):

ME3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22693521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
ME3	NM_001014811.2 linkuse as main transcript	c.1159G>A	p.Glu387Lys	missense_variant	10/14	NP_001014811.1	Q16798-1Q6TCH8
ME3	NM_001161586.3 linkuse as main transcript	c.1159G>A	p.Glu387Lys	missense_variant	11/15	NP_001155058.1	Q16798-1B2R995
ME3	NM_001351934.2 linkuse as main transcript	c.1159G>A	p.Glu387Lys	missense_variant	11/15	NP_001338863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME3	ENST00000543262.6 linkuse as main transcript	c.1159G>A	p.Glu387Lys	missense_variant	11/15	1		ENSP00000440246.1		Q16798-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251420

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

Apr 08, 2024

The c.1159G>A (p.E387K) alteration is located in exon 11 (coding exon 10) of the ME3 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the glutamic acid (E) at amino acid position 387 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.072

T;T;T

Eigen

Benign

-0.029

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.79

N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.81

T;T;T

Sift4G

Benign

0.87

T;T;.

Polyphen

0.0050

B;B;.

Vest4

0.39

MutPred

0.51

Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);

MVP

0.75

MPC

0.57

ClinPred

0.56

GERP RS

5.6

Varity_R

0.49

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over