chr6-83223772-G-A

Variant names:

• chr6-83223772-G-A
• rs116402692
• NM_002395.6:c.1437C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_002395.6(ME1):​c.1437C>T​(p.Leu479Leu) 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
• 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=-0.37).
• BP6: Variant 6-83223772-G-A is Benign according to our data. Variant chr6-83223772-G-A is described in ClinVar as Benign. ClinVar VariationId is 783470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 463 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002395.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	NM_002395.6	MANE Select	c.1437C>T	p.Leu479Leu	synonymous	Exon 12 of 14	NP_002386.1	P48163-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME1	ENST00000369705.4	TSL:1 MANE Select	c.1437C>T	p.Leu479Leu	synonymous	Exon 12 of 14	ENSP00000358719.3	P48163-1
	ME1	ENST00000956348.1		c.1551C>T	p.Leu517Leu	synonymous	Exon 13 of 15	ENSP00000626407.1
	ME1	ENST00000956344.1		c.1491C>T	p.Leu497Leu	synonymous	Exon 13 of 15	ENSP00000626403.1

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

GnomAD2 exomes AF: 0.00147 AC: 369 AN: 250474 AF XY: 0.00117

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 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

African (AFR) AF: 0.0166 AC: 556 AN: 33470

American (AMR) AF: 0.00212 AC: 95 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5760

European-Non Finnish (NFE) AF: 0.000222 AC: 247 AN: 1111746

Other (OTH) AF: 0.00161 AC: 97 AN: 60366

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

African (AFR) AF: 0.0149 AC: 617 AN: 41546

American (AMR) AF: 0.00268 AC: 41 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00227 Hom.: 0

Bravo AF: 0.00566

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.6
DANN	Benign	0.77
PhyloP100		2.8
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs116402692; hg19: chr6-83933491;