chr11-86581480-G-A

Variant names:

• chr11-86581480-G-A
• rs10898503
• NM_001161586.3:c.184-21657C>T

Variant summary

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

The NM_001161586.3(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 NM_001161586.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161586.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	NM_001161586.3	MANE Select	c.184-21657C>T		intron	N/A	NP_001155058.1
	ME3	NM_001014811.2		c.184-21657C>T		intron	N/A	NP_001014811.1
	ME3	NM_001351934.2		c.184-21657C>T		intron	N/A	NP_001338863.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	ENST00000543262.6	TSL:1 MANE Select	c.184-21657C>T		intron	N/A	ENSP00000440246.1
	ME3	ENST00000393324.7	TSL:1	c.184-21657C>T		intron	N/A	ENSP00000376998.2
	ME3	ENST00000323418.10	TSL:5	c.-3-21657C>T		intron	N/A	ENSP00000315255.6

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

African (AFR) AF: 0.204 AC: 8445 AN: 41484

American (AMR) AF: 0.393 AC: 6000 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3470

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5180

South Asian (SAS) AF: 0.311 AC: 1503 AN: 4828

European-Finnish (FIN) AF: 0.626 AC: 6602 AN: 10548

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36835 AN: 67960

Other (OTH) AF: 0.413 AC: 872 AN: 2112

Alfa AF: 0.486 Hom.: 24391

Bravo AF: 0.385

Asia WGS AF: 0.181 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		0.086
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: rs10898503; hg19: chr11-86292522;