11-114312721-G-A

Variant names:

• chr11-114312721-G-A
• rs11569688
• NM_006169.3:c.*244G>A

Variant summary

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

The NM_006169.3(NNMT):​c.*244G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 484,684 control chromosomes in the GnomAD database, including 5,233 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 0.13 (1374 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3859 hom.)
• Consequence: NNMT NM_006169.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 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.*244G>A		3_prime_UTR	Exon 3 of 3	NP_006160.1
	NNMT	NR_164073.1		n.1258G>A		non_coding_transcript_exon	Exon 4 of 4
	NNMT	NM_001372045.1		c.*244G>A		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.*244G>A		3_prime_UTR	Exon 3 of 3	ENSP00000299964.3
	NNMT	ENST00000535401.5	TSL:1	c.*244G>A		3_prime_UTR	Exon 5 of 5	ENSP00000441434.1
	NNMT	ENST00000713573.1		c.*244G>A		3_prime_UTR	Exon 3 of 3	ENSP00000518865.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19306 AN: 152004 Hom.: 1374 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.0892

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.141 AC: 47044 AN: 332562 Hom.: 3859 Cov.: 2 AF XY: 0.142 AC XY: 24217 AN XY: 170902

African (AFR) AF: 0.0736 AC: 815 AN: 11078

American (AMR) AF: 0.0991 AC: 1370 AN: 13822

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 1534 AN: 11252

East Asian (EAS) AF: 0.0336 AC: 928 AN: 27650

South Asian (SAS) AF: 0.0758 AC: 1455 AN: 19196

European-Finnish (FIN) AF: 0.159 AC: 3505 AN: 22044

Middle Eastern (MID) AF: 0.146 AC: 228 AN: 1558

European-Non Finnish (NFE) AF: 0.167 AC: 34344 AN: 205498

Other (OTH) AF: 0.140 AC: 2865 AN: 20464

GnomAD4 genome AF: 0.127 AC: 19305 AN: 152122 Hom.: 1374 Cov.: 32 AF XY: 0.125 AC XY: 9274 AN XY: 74344

African (AFR) AF: 0.0759 AC: 3147 AN: 41486

American (AMR) AF: 0.109 AC: 1663 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3470

East Asian (EAS) AF: 0.0483 AC: 250 AN: 5180

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1692 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11327 AN: 67998

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.0848 Hom.: 148

Bravo AF: 0.123

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		0.37
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: rs11569688; hg19: chr11-114183443;