rs638135

Variant names:

• chr11-86474646-A-G
• rs638135
• NM_001161586.3:c.810-9446T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-86474646-A-G
• chr11-86474646-A-T

Variant summary

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

The NM_001161586.3(ME3):​c.810-9446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,292 control chromosomes in the GnomAD database, including 64,657 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 0.92 (64657 hom., cov: 32)
• Consequence: ME3 NM_001161586.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 1 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]

ENSG00000254733 (HGNC:58438):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	NM_001161586.3	MANE Select	c.810-9446T>C		intron	N/A	NP_001155058.1	Q16798-1
	ME3	NM_001014811.2		c.810-9446T>C		intron	N/A	NP_001014811.1	Q16798-1
	ME3	NM_001351934.2		c.810-9446T>C		intron	N/A	NP_001338863.1	Q16798-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ME3	ENST00000543262.6	TSL:1 MANE Select	c.810-9446T>C		intron	N/A	ENSP00000440246.1	Q16798-1
	ME3	ENST00000393324.7	TSL:1	c.810-9446T>C		intron	N/A	ENSP00000376998.2	Q16798-1
	ME3	ENST00000875290.1		c.969-9446T>C		intron	N/A	ENSP00000545349.1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140097 AN: 152174 Hom.: 64615 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.921 AC: 140196 AN: 152292 Hom.: 64657 Cov.: 32 AF XY: 0.920 AC XY: 68456 AN XY: 74446

African (AFR) AF: 0.893 AC: 37089 AN: 41556

American (AMR) AF: 0.913 AC: 13966 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3809 AN: 5172

South Asian (SAS) AF: 0.892 AC: 4300 AN: 4822

European-Finnish (FIN) AF: 0.972 AC: 10324 AN: 10622

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64417 AN: 68028

Other (OTH) AF: 0.923 AC: 1954 AN: 2116

Alfa AF: 0.931 Hom.: 8523

Bravo AF: 0.912

Asia WGS AF: 0.847 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.065
DANN	Benign	0.73
PhyloP100		-2.3
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: rs638135; hg19: chr11-86185688;