rs1144193

Variant names:

• chr6-83269315-A-G
• rs1144193
• NM_002395.6:c.705-15577T>C

Variant summary

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

The NM_002395.6(ME1):​c.705-15577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,820 control chromosomes in the GnomAD database, including 18,767 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 0.48 (18767 hom., cov: 31)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ME1	NM_002395.6	c.705-15577T>C		intron_variant	Intron 6 of 13	ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.705-15577T>C		intron_variant	Intron 6 of 13	1	NM_002395.6	ENSP00000358719.3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72059 AN: 151710 Hom.: 18733 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.475 AC: 72143 AN: 151820 Hom.: 18767 Cov.: 31 AF XY: 0.471 AC XY: 34912 AN XY: 74152

African (AFR) AF: 0.698 AC: 28849 AN: 41348

American (AMR) AF: 0.487 AC: 7424 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1462 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2119 AN: 5156

South Asian (SAS) AF: 0.295 AC: 1423 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4048 AN: 10550

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25225 AN: 67914

Other (OTH) AF: 0.480 AC: 1010 AN: 2104

Alfa AF: 0.422 Hom.: 1825

Bravo AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.71
PhyloP100		-0.93
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: rs1144193; hg19: chr6-83979034;