rs2290416

Variant names:

• chr8-143575430-G-A
• rs2290416
• NM_145201.6:c.1284C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143575430-G-A
• chr8-143575430-G-C
• chr8-143575430-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145201.6(NAPRT):​c.1284C>T​(p.Gly428Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,591,434 control chromosomes in the GnomAD database, including 6,816 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 0.077 (523 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6293 hom.)
• Consequence: NAPRT NM_145201.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 40 publications found

Genes affected

NAPRT (HGNC:30450): (nicotinate phosphoribosyltransferase) Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

ENSG00000255050 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.338 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.1284C>T	p.Gly428Gly	synonymous_variant	Exon 10 of 13	ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.1284C>T	p.Gly428Gly	synonymous_variant	Exon 10 of 13	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11685 AN: 152064 Hom.: 523 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0895

GnomAD2 exomes AF: 0.0922 AC: 22977 AN: 249258 AF XY: 0.0981

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.0529

Gnomad ASJ exome AF: 0.0979

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.0790

Gnomad NFE exome AF: 0.0892

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0898 AC: 129268 AN: 1439252 Hom.: 6293 Cov.: 38 AF XY: 0.0923 AC XY: 65590 AN XY: 710690

African (AFR) AF: 0.0384 AC: 1270 AN: 33088

American (AMR) AF: 0.0565 AC: 2506 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 2481 AN: 25860

East Asian (EAS) AF: 0.138 AC: 5374 AN: 39030

South Asian (SAS) AF: 0.149 AC: 12789 AN: 85764

European-Finnish (FIN) AF: 0.0755 AC: 3923 AN: 51958

Middle Eastern (MID) AF: 0.131 AC: 745 AN: 5700

European-Non Finnish (NFE) AF: 0.0864 AC: 94593 AN: 1094264

Other (OTH) AF: 0.0943 AC: 5587 AN: 59262

GnomAD4 genome AF: 0.0768 AC: 11690 AN: 152182 Hom.: 523 Cov.: 32 AF XY: 0.0784 AC XY: 5837 AN XY: 74416

African (AFR) AF: 0.0387 AC: 1609 AN: 41528

American (AMR) AF: 0.0785 AC: 1201 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3472

East Asian (EAS) AF: 0.146 AC: 753 AN: 5168

South Asian (SAS) AF: 0.160 AC: 774 AN: 4824

European-Finnish (FIN) AF: 0.0769 AC: 816 AN: 10610

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5943 AN: 67964

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0871 Hom.: 1642

Bravo AF: 0.0731

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.91
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2290416; hg19: chr8-144657600; COSMIC: COSV52786517; COSMIC: COSV52786517;