rs1941404

Positions:

• chr11-114298316-A-G

Variant summary

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

The NM_006169.3(NNMT):​c.362+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 621,058 control chromosomes in the GnomAD database, including 109,824 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 0.59 (26787 hom., cov: 32)
  • Exomes 𝑓: 0.59 (83037 hom.)
• Consequence: NNMT NM_006169.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_006169.3	c.362+158A>G		intron_variant		ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.362+158A>G		intron_variant		1	NM_006169.3	ENSP00000299964.3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89870 AN: 151872 Hom.: 26750 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.591 AC: 277337 AN: 469068 Hom.: 83037 Cov.: 5 AF XY: 0.588 AC XY: 145622 AN XY: 247698

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.609

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.592 AC: 89959 AN: 151990 Hom.: 26787 Cov.: 32 AF XY: 0.589 AC XY: 43734 AN XY: 74312

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.600

Alfa AF: 0.609 Hom.: 38084

Bravo AF: 0.593

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.42

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: rs1941404; hg19: chr11-114169038; COSMIC: COSV55474934;