11-114258335-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372047.1(NNMT):​c.-217+457G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,164 control chromosomes in the GnomAD database, including 7,982 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 0.32 ( 7982 hom., cov: 33)

Consequence

NNMT
NM_001372047.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NNMTNM_001372047.1 linkc.-217+457G>T intron_variant Intron 1 of 4 NP_001358976.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NNMTENST00000535401.5 linkc.-217+457G>T intron_variant Intron 1 of 4 1 ENSP00000441434.1 P40261
NNMTENST00000535185.5 linkn.92+457G>T intron_variant Intron 1 of 2 3
ENSG00000256947ENST00000544925.1 linkn.56+11149C>A intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
AF:
0.316
AC:
48114
AN:
152046
Hom.:
7972
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.290
Gnomad AMI
AF:
0.316
Gnomad AMR
AF:
0.297
Gnomad ASJ
AF:
0.240
Gnomad EAS
AF:
0.552
Gnomad SAS
AF:
0.413
Gnomad FIN
AF:
0.433
Gnomad MID
AF:
0.206
Gnomad NFE
AF:
0.300
Gnomad OTH
AF:
0.282
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.316
AC:
48154
AN:
152164
Hom.:
7982
Cov.:
33
AF XY:
0.324
AC XY:
24091
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.290
Gnomad4 AMR
AF:
0.297
Gnomad4 ASJ
AF:
0.240
Gnomad4 EAS
AF:
0.553
Gnomad4 SAS
AF:
0.413
Gnomad4 FIN
AF:
0.433
Gnomad4 NFE
AF:
0.300
Gnomad4 OTH
AF:
0.287
Alfa
AF:
0.287
Hom.:
10200
Bravo
AF:
0.304
Asia WGS
AF:
0.499
AC:
1731
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.83
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs505978; hg19: chr11-114129057; API