NM_006169.3:c.*110A>G

Variant names:

• chr11-114312587-A-G
• rs4646337
• NM_006169.3:c.*110A>G

Variant summary

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

The NM_006169.3(NNMT):​c.*110A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,065,378 control chromosomes in the GnomAD database, including 18,320 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 0.21 (3420 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14900 hom.)
• Consequence: NNMT NM_006169.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006169.3. 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_006169.3	MANE Select	c.*110A>G		3_prime_UTR	Exon 3 of 3	NP_006160.1
	NNMT	NR_164073.1		n.1124A>G		non_coding_transcript_exon	Exon 4 of 4
	NNMT	NM_001372045.1		c.*110A>G		3_prime_UTR	Exon 4 of 4	NP_001358974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NNMT	ENST00000299964.4	TSL:1 MANE Select	c.*110A>G		3_prime_UTR	Exon 3 of 3	ENSP00000299964.3
	NNMT	ENST00000535401.5	TSL:1	c.*110A>G		3_prime_UTR	Exon 5 of 5	ENSP00000441434.1
	NNMT	ENST00000713573.1		c.*110A>G		3_prime_UTR	Exon 3 of 3	ENSP00000518865.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31297 AN: 151966 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.177 AC: 161223 AN: 913294 Hom.: 14900 Cov.: 12 AF XY: 0.174 AC XY: 80921 AN XY: 464002

African (AFR) AF: 0.287 AC: 6384 AN: 22248

American (AMR) AF: 0.170 AC: 5508 AN: 32326

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 2699 AN: 17880

East Asian (EAS) AF: 0.118 AC: 4358 AN: 36822

South Asian (SAS) AF: 0.123 AC: 7741 AN: 63018

European-Finnish (FIN) AF: 0.167 AC: 5864 AN: 35068

Middle Eastern (MID) AF: 0.183 AC: 555 AN: 3036

European-Non Finnish (NFE) AF: 0.182 AC: 120631 AN: 661104

Other (OTH) AF: 0.179 AC: 7483 AN: 41792

GnomAD4 genome AF: 0.206 AC: 31354 AN: 152084 Hom.: 3420 Cov.: 32 AF XY: 0.205 AC XY: 15219 AN XY: 74346

African (AFR) AF: 0.284 AC: 11761 AN: 41460

American (AMR) AF: 0.205 AC: 3126 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3470

East Asian (EAS) AF: 0.136 AC: 705 AN: 5170

South Asian (SAS) AF: 0.124 AC: 596 AN: 4814

European-Finnish (FIN) AF: 0.174 AC: 1843 AN: 10600

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12211 AN: 67998

Other (OTH) AF: 0.214 AC: 450 AN: 2106

Alfa AF: 0.185 Hom.: 4242

Bravo AF: 0.212

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.046
DANN	Benign	0.56
PhyloP100		-3.5
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: rs4646337; hg19: chr11-114183309;