rs3798886

Variant names:

• chr6-83421807-G-A
• rs3798886
• NM_002395.6:c.78+9070C>T

Variant summary

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

The NM_002395.6(ME1):​c.78+9070C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,034 control chromosomes in the GnomAD database, including 14,925 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 0.43 (14925 hom., cov: 32)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 4 publications found

Genes affected

ME1 (HGNC:6983): (malic enzyme 1) This gene encodes a cytosolic, NADP-dependent enzyme that generates NADPH for fatty acid biosynthesis. The activity of this enzyme, the reversible oxidative decarboxylation of malate, links the glycolytic and citric acid cycles. The regulation of expression for this gene is complex. Increased expression can result from elevated levels of thyroid hormones or by higher proportions of carbohydrates in the diet. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.78+9070C>T		intron_variant	Intron 1 of 13	ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.78+9070C>T		intron_variant	Intron 1 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64604 AN: 151916 Hom.: 14894 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.425 AC: 64679 AN: 152034 Hom.: 14925 Cov.: 32 AF XY: 0.420 AC XY: 31214 AN XY: 74314

African (AFR) AF: 0.590 AC: 24457 AN: 41468

American (AMR) AF: 0.507 AC: 7736 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1801 AN: 5162

South Asian (SAS) AF: 0.253 AC: 1216 AN: 4812

European-Finnish (FIN) AF: 0.323 AC: 3417 AN: 10588

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23042 AN: 67956

Other (OTH) AF: 0.453 AC: 955 AN: 2110

Alfa AF: 0.362 Hom.: 6235

Bravo AF: 0.457

Asia WGS AF: 0.332 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		-0.048
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: rs3798886; hg19: chr6-84131526;