chr11-86460412-A-G

Position:

• chr11-86460412-A-G

Variant summary

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

The NM_006680.3(ME3):​c.919+4679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,176 control chromosomes in the GnomAD database, including 56,081 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 0.86 (56081 hom., cov: 32)
• Consequence: ME3 NM_006680.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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]

ME3 (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 = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME3	NM_001014811.2	c.919+4679T>C		intron_variant			NP_001014811.1
ME3	NM_001161586.3	c.919+4679T>C		intron_variant			NP_001155058.1
ME3	NM_001351934.2	c.919+4679T>C		intron_variant			NP_001338863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME3	ENST00000543262.6	c.919+4679T>C		intron_variant		1		ENSP00000440246.1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130494 AN: 152058 Hom.: 56044 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.858 AC: 130589 AN: 152176 Hom.: 56081 Cov.: 32 AF XY: 0.858 AC XY: 63804 AN XY: 74392

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.856

Alfa AF: 0.860 Hom.: 74074

Bravo AF: 0.851

Asia WGS AF: 0.828 AC: 2881 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	0.14
DANN	Benign	0.53

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: rs618513; hg19: chr11-86171454;