rs3819100

Variant names:

• chr11-114296754-T-C
• rs3819100
• NM_006169.3:c.154+44T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.81).
• 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 rank	MANE	Protein	UniProt
NNMT	NM_006169.3	c.154+44T>C		intron_variant	Intron 1 of 2	ENST00000299964.4	NP_006160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000299964.4	c.154+44T>C		intron_variant	Intron 1 of 2	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

GnomAD2 exomes AF: 0.310 AC: 76900 AN: 248296 AF XY: 0.314

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 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

African (AFR) AF: 0.160 AC: 5280 AN: 33082

American (AMR) AF: 0.309 AC: 13720 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9223 AN: 25840

East Asian (EAS) AF: 0.514 AC: 20350 AN: 39604

South Asian (SAS) AF: 0.374 AC: 31970 AN: 85374

European-Finnish (FIN) AF: 0.318 AC: 16920 AN: 53206

Middle Eastern (MID) AF: 0.288 AC: 1549 AN: 5382

European-Non Finnish (NFE) AF: 0.278 AC: 305302 AN: 1098844

Other (OTH) AF: 0.291 AC: 17417 AN: 59790

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

African (AFR) AF: 0.166 AC: 6886 AN: 41532

American (AMR) AF: 0.265 AC: 4060 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2436 AN: 5172

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4816

European-Finnish (FIN) AF: 0.330 AC: 3499 AN: 10590

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18856 AN: 67988

Other (OTH) AF: 0.250 AC: 530 AN: 2116

Alfa AF: 0.277 Hom.: 10748

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
PhyloP100		-0.59
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3819100; hg19: chr11-114167476; COSMIC: COSV55472947; COSMIC: COSV55472947;