11-114311785-C-T

Position:

• chr11-114311785-C-T

Variant summary

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

The NM_006169.3(NNMT):​c.363-260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,072 control chromosomes in the GnomAD database, including 34,434 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 0.65 (34434 hom., cov: 32)
• Consequence: NNMT NM_006169.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

NNMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_006169.3	c.363-260C>T		intron_variant		ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.363-260C>T		intron_variant		1	NM_006169.3	ENSP00000299964.3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99069 AN: 151954 Hom.: 34425 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.652 AC: 99097 AN: 152072 Hom.: 34434 Cov.: 32 AF XY: 0.655 AC XY: 48704 AN XY: 74326

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.659

Alfa AF: 0.738 Hom.: 61040

Bravo AF: 0.640

Asia WGS AF: 0.730 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.78

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: rs2852425; hg19: chr11-114182507;