NM_017881.3:c.496+886A>G

Variant names:

• chr9-75068110-T-C
• rs7021664
• NM_017881.3:c.496+886A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017881.3(NMRK1):​c.496+886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,186 control chromosomes in the GnomAD database, including 67,842 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 0.94 (67842 hom., cov: 30)
• Consequence: NMRK1 NM_017881.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 2 publications found

Genes affected

NMRK1 (HGNC:26057): (nicotinamide riboside kinase 1) Nicotinamide adenine dinucleotide (NAD+) is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADP-ribosyl groups used in various reactions. Nicotinic acid and nicotinamide, collectively known as niacin, are the vitamin precursors of NAD+. Nicotinamide riboside kinases, such as NRK1, function to synthesize NAD+ through nicotinamide mononucleotide using nicotinamide riboside as the precursor (Bieganowski and Brenner, 2004 [PubMed 15137942]).[supplied by OMIM, Mar 2008]

NMRK1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017881.3. 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
	NMRK1	NM_017881.3	MANE Select	c.496+886A>G		intron	N/A	NP_060351.1
	NMRK1	NM_001330678.2		c.508+886A>G		intron	N/A	NP_001317607.1
	NMRK1	NM_001330679.2		c.508+886A>G		intron	N/A	NP_001317608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMRK1	ENST00000361092.9	TSL:1 MANE Select	c.496+886A>G		intron	N/A	ENSP00000354387.4
	NMRK1	ENST00000376808.8	TSL:1	c.424+886A>G		intron	N/A	ENSP00000366004.4
	NMRK1	ENST00000908065.1		c.497-843A>G		intron	N/A	ENSP00000578124.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143494 AN: 152068 Hom.: 67785 Cov.: 30

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.936

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.944 AC: 143611 AN: 152186 Hom.: 67842 Cov.: 30 AF XY: 0.943 AC XY: 70101 AN XY: 74376

African (AFR) AF: 0.982 AC: 40793 AN: 41524

American (AMR) AF: 0.946 AC: 14475 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3169 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5166

South Asian (SAS) AF: 0.915 AC: 4403 AN: 4810

European-Finnish (FIN) AF: 0.905 AC: 9577 AN: 10588

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62949 AN: 68018

Other (OTH) AF: 0.936 AC: 1976 AN: 2110

Alfa AF: 0.931 Hom.: 116878

Bravo AF: 0.950

Asia WGS AF: 0.964 AC: 3352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.65
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs7021664; hg19: chr9-77683026;