rs507211

Variant names:

• chr11-86665697-G-A
• rs507211
• NM_001161586.3:c.183+6065C>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.183+6065C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,098 control chromosomes in the GnomAD database, including 5,765 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 0.27 (5765 hom., cov: 33)
• Consequence: ME3 NM_001161586.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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.183+6065C>T		intron	N/A	NP_001155058.1
	ME3	NM_001014811.2		c.183+6065C>T		intron	N/A	NP_001014811.1
	ME3	NM_001351934.2		c.183+6065C>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.183+6065C>T		intron	N/A	ENSP00000440246.1
	ME3	ENST00000393324.7	TSL:1	c.183+6065C>T		intron	N/A	ENSP00000376998.2
	ME3	ENST00000323418.10	TSL:5	c.-4+6065C>T		intron	N/A	ENSP00000315255.6

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41466 AN: 151980 Hom.: 5752 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.273 AC: 41504 AN: 152098 Hom.: 5765 Cov.: 33 AF XY: 0.269 AC XY: 20007 AN XY: 74360

African (AFR) AF: 0.302 AC: 12531 AN: 41482

American (AMR) AF: 0.229 AC: 3494 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1012 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1846 AN: 5172

South Asian (SAS) AF: 0.266 AC: 1284 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2369 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18252 AN: 67970

Other (OTH) AF: 0.246 AC: 519 AN: 2114

Alfa AF: 0.270 Hom.: 23718

Bravo AF: 0.274

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		0.41
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: rs507211; hg19: chr11-86376739;