11-114312587-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.*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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNMT	NM_006169.3	c.*110A>G		3_prime_UTR_variant	3/3	ENST00000299964.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NNMT	ENST00000299964.4	c.*110A>G		3_prime_UTR_variant	3/3	1	NM_006169.3	P1
NNMT	ENST00000535401.5	c.*110A>G		3_prime_UTR_variant	5/5	1		P1
	ENST00000544925.1	n.51-43098T>C		intron_variant, non_coding_transcript_variant		5
NNMT	ENST00000713573.1	c.*110A>G		3_prime_UTR_variant	3/3			P1

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

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.179

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

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.214

Alfa AF: 0.183 Hom.: 3503

Bravo AF: 0.212

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.046
Dann	Benign	0.56

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: rs4646337; hg19: chr11-114183309;