ENST00000535401.5:c.-129-3146A>G

Variant names:

• chr11-114293282-A-G
• rs2852432
• ENST00000535401.5:c.-129-3146A>G

Variant summary

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

The ENST00000535401.5(NNMT):​c.-129-3146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,872 control chromosomes in the GnomAD database, including 31,274 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 0.62 (31274 hom., cov: 30)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 7 publications found

Genes affected

NNMT (HGNC:7861): (nicotinamide N-methyltransferase) N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver. This gene encodes the protein responsible for this enzymatic activity which uses S-adenosyl methionine as the methyl donor. [provided by RefSeq, Jul 2008]

ENSG00000256947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535401.5. 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
	NNMT	NM_001372047.1		c.-129-3146A>G		intron	N/A	NP_001358976.1
	NNMT	NR_164073.1		n.374-4669A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000535401.5	TSL:1	c.-129-3146A>G		intron	N/A	ENSP00000441434.1
	NNMT	ENST00000541090.1	TSL:3	n.188-18763A>G		intron	N/A
	ENSG00000256947	ENST00000544925.1	TSL:5	n.51-23793T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94496 AN: 151752 Hom.: 31271 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.622 AC: 94522 AN: 151872 Hom.: 31274 Cov.: 30 AF XY: 0.618 AC XY: 45868 AN XY: 74204

African (AFR) AF: 0.384 AC: 15925 AN: 41432

American (AMR) AF: 0.714 AC: 10911 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3468

East Asian (EAS) AF: 0.587 AC: 2987 AN: 5086

South Asian (SAS) AF: 0.557 AC: 2678 AN: 4812

European-Finnish (FIN) AF: 0.661 AC: 6986 AN: 10570

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50429 AN: 67918

Other (OTH) AF: 0.652 AC: 1372 AN: 2104

Alfa AF: 0.699 Hom.: 56640

Bravo AF: 0.623

Asia WGS AF: 0.565 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.85
PhyloP100		-0.10
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: rs2852432; hg19: chr11-114164004;