11-86477110-A-G

Variant names:

• chr11-86477110-A-G
• rs1870323
• ENST00000393324.7:c.809+10227T>C

Variant summary

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

The ENST00000543262.6(ME3):​c.809+10227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,080 control chromosomes in the GnomAD database, including 11,184 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 0.37 (11184 hom., cov: 32)
• Consequence: ME3 ENST00000543262.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 10 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME3	NM_001014811.2	c.809+10227T>C		intron_variant	Intron 6 of 13		NP_001014811.1
ME3	NM_001161586.3	c.809+10227T>C		intron_variant	Intron 7 of 14		NP_001155058.1
ME3	NM_001351934.2	c.809+10227T>C		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+10227T>C		intron_variant	Intron 7 of 14	1		ENSP00000440246.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56942 AN: 151962 Hom.: 11184 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.375 AC: 56958 AN: 152080 Hom.: 11184 Cov.: 32 AF XY: 0.373 AC XY: 27702 AN XY: 74336

African (AFR) AF: 0.290 AC: 12053 AN: 41494

American (AMR) AF: 0.355 AC: 5424 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1272 AN: 5176

South Asian (SAS) AF: 0.448 AC: 2154 AN: 4808

European-Finnish (FIN) AF: 0.414 AC: 4376 AN: 10570

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28901 AN: 67970

Other (OTH) AF: 0.390 AC: 823 AN: 2112

Alfa AF: 0.400 Hom.: 16414

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.42
PhyloP100		0.074
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: rs1870323; hg19: chr11-86188152;