NM_001161586.3:c.183+35353C>G

Variant names:

• chr11-86636409-G-C
• rs7940523
• NM_001161586.3:c.183+35353C>G

Variant summary

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

The NM_001161586.3(ME3):​c.183+35353C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,238 control chromosomes in the GnomAD database, including 692 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 0.094 (692 hom., cov: 32)
• Consequence: ME3 NM_001161586.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 2 publications found

Genes affected

ME3 (HGNC:6985): (malic enzyme 3) Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161586.3. 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
	ME3	NM_001161586.3	MANE Select	c.183+35353C>G		intron	N/A	NP_001155058.1
	ME3	NM_001014811.2		c.183+35353C>G		intron	N/A	NP_001014811.1
	ME3	NM_001351934.2		c.183+35353C>G		intron	N/A	NP_001338863.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	ENST00000543262.6	TSL:1 MANE Select	c.183+35353C>G		intron	N/A	ENSP00000440246.1
	ME3	ENST00000393324.7	TSL:1	c.183+35353C>G		intron	N/A	ENSP00000376998.2
	ME3	ENST00000323418.10	TSL:5	c.-4+35353C>G		intron	N/A	ENSP00000315255.6

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14264 AN: 152120 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0937 AC: 14269 AN: 152238 Hom.: 692 Cov.: 32 AF XY: 0.0933 AC XY: 6944 AN XY: 74454

African (AFR) AF: 0.0948 AC: 3937 AN: 41534

American (AMR) AF: 0.0806 AC: 1233 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5188

South Asian (SAS) AF: 0.126 AC: 605 AN: 4818

European-Finnish (FIN) AF: 0.0640 AC: 679 AN: 10606

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7205 AN: 68008

Other (OTH) AF: 0.109 AC: 229 AN: 2110

Alfa AF: 0.100 Hom.: 100

Bravo AF: 0.0929

Asia WGS AF: 0.0670 AC: 233 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.45
PhyloP100		-0.57
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: rs7940523; hg19: chr11-86347451;