rs4646335

Positions:

• chr11-114296220-A-T

Variant summary

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

The ENST00000535401.5(NNMT):​c.-129-208A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 203,204 control chromosomes in the GnomAD database, including 4,393 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 0.17 (2893 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1500 hom.)
• Consequence: NNMT ENST00000535401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NNMT	NM_001372045.1	c.-129-208A>T		intron_variant			NP_001358974.1
NNMT	NM_001372046.1	c.-126-211A>T		intron_variant			NP_001358975.1
NNMT	NM_001372047.1	c.-129-208A>T		intron_variant			NP_001358976.1
NNMT	NR_164073.1	n.374-1731A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NNMT	ENST00000535401.5	c.-129-208A>T		intron_variant		1		ENSP00000441434	P1
	ENST00000544925.1	n.51-26731T>A		intron_variant, non_coding_transcript_variant		5
NNMT	ENST00000713573.1	c.-337A>T		5_prime_UTR_variant	1/3			ENSP00000518865	P1
NNMT	ENST00000541090.1	n.188-15825A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26115 AN: 151862 Hom.: 2890 Cov.: 31

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.219 AC: 11239 AN: 51224 Hom.: 1500 Cov.: 0 AF XY: 0.221 AC XY: 5781 AN XY: 26212

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.172 AC: 26120 AN: 151980 Hom.: 2893 Cov.: 31 AF XY: 0.178 AC XY: 13249 AN XY: 74278

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.150

Alfa AF: 0.205 Hom.: 1989

Bravo AF: 0.162

Asia WGS AF: 0.253 AC: 879 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	5.6
DANN	Benign	0.66

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: rs4646335; hg19: chr11-114166942;