rs12797615

chr11-86555641-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393324.7(ME3):c.467+912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,150 control chromosomes in the GnomAD database, including 4,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4692 hom., cov: 32)
• Consequence: ME3 ENST00000393324.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME3	NM_001161586.3	c.467+912A>G		intron_variant		ENST00000543262.6
ME3	NR_172888.1	n.774+912A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME3	ENST00000543262.6	c.467+912A>G		intron_variant		1	NM_001161586.3	P1
	ENST00000524610.1	n.269-67084T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34378 AN: 152032 Hom.: 4693 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.241

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34390 AN: 152150 Hom.: 4692 Cov.: 32 AF XY: 0.223 AC XY: 16570 AN XY: 74378

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.239

Alfa AF: 0.294 Hom.: 7697

Bravo AF: 0.218

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.28
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs12797615; hg19: chr11-86266683;