rs896954

Positions:

• chr8-143577876-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145201.6(NAPRT):​c.294C>T​(p.Ala98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,611,946 control chromosomes in the GnomAD database, including 24,848 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 0.15 (2001 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22847 hom.)
• Consequence: NAPRT NM_145201.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-0.284 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.294C>T	p.Ala98=	synonymous_variant	2/13	ENST00000449291.7
NAPRT	NM_001286829.2	c.294C>T	p.Ala98=	synonymous_variant	2/13
NAPRT	NM_001363145.1	c.294C>T	p.Ala98=	synonymous_variant	2/12
NAPRT	NM_001363146.1	c.-275C>T		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.294C>T	p.Ala98=	synonymous_variant	2/13	1	NM_145201.6	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23414 AN: 152056 Hom.: 2001 Cov.: 33

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.182 AC: 44532 AN: 244450 Hom.: 4383 AF XY: 0.184 AC XY: 24637 AN XY: 133540

Gnomad AFR exome AF: 0.0935

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.111

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.173 AC: 252170 AN: 1459772 Hom.: 22847 Cov.: 39 AF XY: 0.175 AC XY: 127133 AN XY: 726140

Gnomad4 AFR exome AF: 0.0959

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.154 AC: 23414 AN: 152174 Hom.: 2001 Cov.: 33 AF XY: 0.157 AC XY: 11706 AN XY: 74396

Gnomad4 AFR AF: 0.0940

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.171

Alfa AF: 0.163 Hom.: 2021

Bravo AF: 0.149

Asia WGS AF: 0.181 AC: 626 AN: 3476

EpiCase AF: 0.166

EpiControl AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs896954; hg19: chr8-144660046; COSMIC: COSV52786079; COSMIC: COSV52786079;