Genetic Variant NNMT:c.-152G>T (chr11-114262912-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372047.1(NNMT):c.-152G>T variant causes a 5 prime UTR premature start codon gain 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
NM_001372047.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.620

Publications

4 publications found

Variant links:

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]

NNMT links:

ENSG00000256947 (HGNC:):

ENSG00000256947 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372047.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NNMT	NM_001372047.1	c.-152G>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001358976.1
NNMT	NM_001372047.1	c.-152G>T	5_prime_UTR	Exon 2 of 5	NP_001358976.1
NNMT	NR_164073.1	n.351G>T	non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NNMT	ENST00000535401.5	TSL:1	c.-152G>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000441434.1
NNMT	ENST00000535401.5	TSL:1	c.-152G>T	5_prime_UTR	Exon 2 of 5	ENSP00000441434.1
NNMT	ENST00000858477.1		c.-152G>T	5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000528536.1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40616

AN:

151958

Hom.:

6182

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.289

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.267

AC:

40671

AN:

152076

Hom.:

6199

Cov.:

AF XY:

0.276

AC XY:

20508

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.406

AC:

16845

AN:

41440

American (AMR)

AF:

0.272

AC:

4157

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

600

AN:

3470

East Asian (EAS)

AF:

0.318

AC:

1642

AN:

5164

South Asian (SAS)

AF:

0.328

AC:

1582

AN:

4824

European-Finnish (FIN)

AF:

0.299

AC:

3163

AN:

10580

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11989

AN:

67980

Other (OTH)

AF:

0.239

AC:

506

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1445

2889

4334

5778

7223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.249

Hom.:

995

Bravo

AF:

0.268

Asia WGS

AF:

0.325

AC:

1128

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

1.0

(source)

DANN

Benign

0.67

PhyloP100

-0.62

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over