ME3 p.Lys324Asn

Variant names:

• chr11-86450346-C-A
• NM_001161586.3:c.972G>T
• ME3 p.Lys324Asn

Your query was ambiguous. Multiple possible variants found:

• chr11-86450346-C-A
• chr11-86450346-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001161586.3(ME3):​c.972G>T​(p.Lys324Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ME3 NM_001161586.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• 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:58438):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3885433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161586.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	NM_001161586.3	MANE Select	c.972G>T	p.Lys324Asn	missense	Exon 9 of 15	NP_001155058.1	Q16798-1
	ME3	NM_001014811.2		c.972G>T	p.Lys324Asn	missense	Exon 8 of 14	NP_001014811.1	Q16798-1
	ME3	NM_001351934.2		c.972G>T	p.Lys324Asn	missense	Exon 9 of 15	NP_001338863.1	Q16798-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	ENST00000543262.6	TSL:1 MANE Select	c.972G>T	p.Lys324Asn	missense	Exon 9 of 15	ENSP00000440246.1	Q16798-1
	ME3	ENST00000393324.7	TSL:1	c.972G>T	p.Lys324Asn	missense	Exon 8 of 14	ENSP00000376998.2	Q16798-1
	ME3	ENST00000875290.1		c.1131G>T	p.Lys377Asn	missense	Exon 10 of 16	ENSP00000545349.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.023
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Varity_R		0.16
gMVP		0.76
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-86161388;