chr11-86441296-T-A

Variant names:

• chr11-86441296-T-A
• ENST00000393324.7:c.1798A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000543262.6(ME3):​c.1798A>T​(p.Asn600Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: ME3 ENST00000543262.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 0 publications found

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]

ENSG00000254733 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1328269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME3	NM_001014811.2	c.1798A>T	p.Asn600Tyr	missense_variant	Exon 14 of 14		NP_001014811.1
ME3	NM_001161586.3	c.1798A>T	p.Asn600Tyr	missense_variant	Exon 15 of 15		NP_001155058.1
ME3	NM_001351934.2	c.1798A>T	p.Asn600Tyr	missense_variant	Exon 15 of 15		NP_001338863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME3	ENST00000393324.7	c.1798A>T	p.Asn600Tyr	missense_variant	Exon 14 of 14	1		ENSP00000376998.2
ME3	ENST00000543262.6	c.1798A>T	p.Asn600Tyr	missense_variant	Exon 15 of 15	1		ENSP00000440246.1
ENSG00000254733	ENST00000524610.2	n.383+8654T>A		intron_variant	Intron 2 of 2	3
ENSG00000254733	ENST00000758792.1	n.423+8654T>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1798A>T (p.N600Y) alteration is located in exon 15 (coding exon 14) of the ME3 gene. This alteration results from a A to T substitution at nucleotide position 1798, causing the asparagine (N) at amino acid position 600 to be replaced by a tyrosine (Y). 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	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		3.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.066
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.084	B;B
Vest4		0.19
MutPred		0.21		Loss of disorder (P = 0.0537);Loss of disorder (P = 0.0537);
MVP		0.68
MPC		0.65
ClinPred		0.79	D
GERP RS		3.8
Varity_R		0.085
gMVP		0.51
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr11-86152338;