rs3819100

Positions:

• chr11-114296754-T-C

Variant summary

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

The NM_006169.3(NNMT):​c.154+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,597,728 control chromosomes in the GnomAD database, including 69,466 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 0.26 (5596 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63870 hom.)
• Consequence: NNMT NM_006169.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_006169.3	c.154+44T>C		intron_variant		ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.154+44T>C		intron_variant		1	NM_006169.3	ENSP00000299964.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39737 AN: 152062 Hom.: 5596 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.310 AC: 76900 AN: 248296 Hom.: 12613 AF XY: 0.314 AC XY: 42055 AN XY: 134058

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.475

Gnomad SAS exome AF: 0.374

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.292 AC: 421731 AN: 1445548 Hom.: 63870 Cov.: 26 AF XY: 0.295 AC XY: 212164 AN XY: 719262

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.261 AC: 39734 AN: 152180 Hom.: 5596 Cov.: 32 AF XY: 0.266 AC XY: 19818 AN XY: 74390

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.250

Alfa AF: 0.280 Hom.: 8853

Bravo AF: 0.253

Asia WGS AF: 0.352 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3819100; hg19: chr11-114167476; COSMIC: COSV55472947; COSMIC: COSV55472947;