11-114312587-A-T

Variant names:

• chr11-114312587-A-T
• rs4646337
• NM_006169.3:c.*110A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006169.3(NNMT):​c.*110A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 914,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: NNMT NM_006169.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.*110A>T		3_prime_UTR	Exon 3 of 3	NP_006160.1
	NNMT	NR_164073.1		n.1124A>T		non_coding_transcript_exon	Exon 4 of 4
	NNMT	NM_001372045.1		c.*110A>T		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.*110A>T		3_prime_UTR	Exon 3 of 3	ENSP00000299964.3
	NNMT	ENST00000535401.5	TSL:1	c.*110A>T		3_prime_UTR	Exon 5 of 5	ENSP00000441434.1
	NNMT	ENST00000713573.1		c.*110A>T		3_prime_UTR	Exon 3 of 3	ENSP00000518865.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000437 AC: 4 AN: 914522 Hom.: 0 Cov.: 12 AF XY: 0.00000861 AC XY: 4 AN XY: 464574

African (AFR) AF: 0.00 AC: 0 AN: 22276

American (AMR) AF: 0.00 AC: 0 AN: 32354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17894

East Asian (EAS) AF: 0.00 AC: 0 AN: 36834

South Asian (SAS) AF: 0.00 AC: 0 AN: 63046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3036

European-Non Finnish (NFE) AF: 0.00000604 AC: 4 AN: 662154

Other (OTH) AF: 0.00 AC: 0 AN: 41834

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.033
DANN	Benign	0.56
PhyloP100		-3.5

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: rs4646337; hg19: chr11-114183309;