chr11-86555641-T-C

Variant names:

• chr11-86555641-T-C
• rs12797615
• ENST00000393324.7:c.467+912A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-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 rank	MANE	Protein	UniProt
ME3	NM_001014811.2	c.467+912A>G		intron_variant	Intron 3 of 13		NP_001014811.1
ME3	NM_001161586.3	c.467+912A>G		intron_variant	Intron 4 of 14		NP_001155058.1
ME3	NM_001351934.2	c.467+912A>G		intron_variant	Intron 4 of 14		NP_001338863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME3	ENST00000543262.6	c.467+912A>G		intron_variant	Intron 4 of 14	1		ENSP00000440246.1

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

African (AFR) AF: 0.0850 AC: 3530 AN: 41534

American (AMR) AF: 0.263 AC: 4017 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3468

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5184

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4814

European-Finnish (FIN) AF: 0.254 AC: 2692 AN: 10580

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21035 AN: 67974

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.287 Hom.: 9227

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
PhyloP100		-0.84
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: rs12797615; hg19: chr11-86266683;