chr11-86480651-C-T

Variant names:

• chr11-86480651-C-T
• rs632538
• ENST00000393324.7:c.809+6686G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393324.7(ME3):​c.809+6686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,206 control chromosomes in the GnomAD database, including 54,278 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 0.84 (54278 hom., cov: 32)
• Consequence: ME3 ENST00000393324.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME3	NM_001014811.2	c.809+6686G>A		intron_variant	Intron 6 of 13		NP_001014811.1
ME3	NM_001161586.3	c.809+6686G>A		intron_variant	Intron 7 of 14		NP_001155058.1
ME3	NM_001351934.2	c.809+6686G>A		intron_variant	Intron 7 of 14		NP_001338863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME3	ENST00000543262.6	c.809+6686G>A		intron_variant	Intron 7 of 14	1		ENSP00000440246.1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128235 AN: 152088 Hom.: 54251 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.843 AC: 128318 AN: 152206 Hom.: 54278 Cov.: 32 AF XY: 0.845 AC XY: 62859 AN XY: 74422

African (AFR) AF: 0.788 AC: 32721 AN: 41506

American (AMR) AF: 0.838 AC: 12804 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2933 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3685 AN: 5174

South Asian (SAS) AF: 0.783 AC: 3781 AN: 4826

European-Finnish (FIN) AF: 0.940 AC: 9965 AN: 10604

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59546 AN: 68024

Other (OTH) AF: 0.853 AC: 1800 AN: 2110

Alfa AF: 0.831 Hom.: 3296

Bravo AF: 0.833

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.48
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs632538; hg19: chr11-86191693;