6-83397515-C-T

Variant names:

• chr6-83397515-C-T
• rs13215578
• NM_002395.6:c.362+852G>A

Variant summary

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

The ENST00000369705.4(ME1):​c.362+852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,030 control chromosomes in the GnomAD database, including 7,930 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 0.31 (7930 hom., cov: 32)
• Consequence: ME1 ENST00000369705.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369705.4. 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
	ME1	NM_002395.6	MANE Select	c.362+852G>A		intron	N/A	NP_002386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	ENST00000369705.4	TSL:1 MANE Select	c.362+852G>A		intron	N/A	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47836 AN: 151912 Hom.: 7917 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.315 AC: 47866 AN: 152030 Hom.: 7930 Cov.: 32 AF XY: 0.311 AC XY: 23086 AN XY: 74312

African (AFR) AF: 0.270 AC: 11190 AN: 41470

American (AMR) AF: 0.455 AC: 6945 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1380 AN: 5178

South Asian (SAS) AF: 0.205 AC: 991 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3030 AN: 10564

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21674 AN: 67954

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.316 Hom.: 1561

Bravo AF: 0.335

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.62
PhyloP100		0.17
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: rs13215578; hg19: chr6-84107234; COSMIC: COSV63838152; COSMIC: COSV63838152;