6-83223772-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_002395.6(ME1):c.1437C>T(p.Leu479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,613,732 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (5 hom.)
• Consequence: ME1 NM_002395.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 6-83223772-G-A is Benign according to our data. Variant chr6-83223772-G-A is described in ClinVar as [Benign]. Clinvar id is 783470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00069 (1009/1461470) while in subpopulation AFR AF= 0.0166 (556/33470). AF 95% confidence interval is 0.0155. There are 5 homozygotes in gnomad4_exome. There are 463 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME1	NM_002395.6	c.1437C>T	p.Leu479=	synonymous_variant	12/14	ENST00000369705.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME1	ENST00000369705.4	c.1437C>T	p.Leu479=	synonymous_variant	12/14	1	NM_002395.6	P1

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 689 AN: 152144 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00147 AC: 369 AN: 250474 Hom.: 3 AF XY: 0.00117 AC XY: 158 AN XY: 135352

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.000690 AC: 1009 AN: 1461470 Hom.: 5 Cov.: 31 AF XY: 0.000637 AC XY: 463 AN XY: 727046

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000222

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00453 AC: 689 AN: 152262 Hom.: 4 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74458

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00566

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	6.6
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116402692; hg19: chr6-83933491;