11-114262912-G-T

Variant summary

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

The ENST00000535401.5(NNMT):c.-152G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,122 control chromosomes in the GnomAD database, including 6,201 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 0.27 (6199 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2 hom.)
• Consequence: NNMT ENST00000535401.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NNMT	NM_001372047.1	c.-152G>T		5_prime_UTR_variant	2/5
NNMT	NR_164073.1	n.351G>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NNMT	ENST00000535401.5	c.-152G>T		5_prime_UTR_variant	2/5	1		P1
	ENST00000544925.1	n.56+6572C>A		intron_variant, non_coding_transcript_variant		5
NNMT	ENST00000535185.5	n.157G>T		non_coding_transcript_exon_variant	2/3	3
NNMT	ENST00000541090.1	n.25G>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40616 AN: 151958 Hom.: 6182 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.261 AC: 12 AN: 46 Hom.: 2 Cov.: 0 AF XY: 0.289 AC XY: 11 AN XY: 38

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.267 AC: 40671 AN: 152076 Hom.: 6199 Cov.: 32 AF XY: 0.276 AC XY: 20508 AN XY: 74334

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.239

Alfa AF: 0.243 Hom.: 913

Bravo AF: 0.268

Asia WGS AF: 0.325 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.0
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10891639; hg19: chr11-114133634;