rs7940523

chr11-86636409-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393324.7(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 ENST00000393324.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ME3	NM_001161586.3	c.183+35353C>G		intron_variant		ENST00000543262.6
ME3	NR_172888.1	n.490+35353C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ME3	ENST00000543262.6	c.183+35353C>G		intron_variant		1	NM_001161586.3	P1

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

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0640

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.109

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.41
Dann	Benign	0.45

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: rs7940523; hg19: chr11-86347451;