rs3839445

Positions:

• chr6-83307790-CTCTA-C
• chr6-83307790-CTCTA-CTCTATCTA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002395.6(ME1):​c.704+7516_704+7519del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,848 control chromosomes in the GnomAD database, including 6,054 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (6054 hom., cov: 30)
• Consequence: ME1 NM_002395.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ME1	NM_002395.6	c.704+7516_704+7519del		intron_variant		ENST00000369705.4	NP_002386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ME1	ENST00000369705.4	c.704+7516_704+7519del		intron_variant		1	NM_002395.6	ENSP00000358719	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27367 AN: 151728 Hom.: 6018 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.181 AC: 27463 AN: 151848 Hom.: 6054 Cov.: 30 AF XY: 0.178 AC XY: 13235 AN XY: 74254

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.148

Alfa AF: 0.119 Hom.: 462

Bravo AF: 0.201

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3839445; hg19: chr6-84017509;