11-86581480-G-A

Position:

• chr11-86581480-G-A

Variant summary

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

The ENST00000393324.7(ME3):​c.184-21657C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,054 control chromosomes in the GnomAD database, including 15,218 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 0.41 (15218 hom., cov: 32)
• Consequence: ME3 ENST00000393324.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME3	NM_001161586.3	c.184-21657C>T		intron_variant		ENST00000543262.6
ME3	NR_172888.1	n.491-21657C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME3	ENST00000543262.6	c.184-21657C>T		intron_variant		1	NM_001161586.3	P1
	ENST00000524610.1	n.269-41245G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62849 AN: 151936 Hom.: 15216 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.414 AC: 62884 AN: 152054 Hom.: 15218 Cov.: 32 AF XY: 0.412 AC XY: 30648 AN XY: 74304

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.413

Alfa AF: 0.500 Hom.: 19391

Bravo AF: 0.385

Asia WGS AF: 0.181 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.71

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: rs10898503; hg19: chr11-86292522;