rs896954

Variant names:

• chr8-143577876-G-A
• rs896954
• NM_145201.6:c.294C>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.294C>T​(p.Ala98Ala) 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
• Publications: 24 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.294C>T	p.Ala98Ala	synonymous_variant	Exon 2 of 13	ENST00000449291.7	NP_660202.3
NAPRT	NM_001286829.2	c.294C>T	p.Ala98Ala	synonymous_variant	Exon 2 of 13		NP_001273758.1
NAPRT	NM_001363145.1	c.294C>T	p.Ala98Ala	synonymous_variant	Exon 2 of 12		NP_001350074.1
NAPRT	NM_001363146.1	c.-275C>T		5_prime_UTR_variant	Exon 2 of 12		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.294C>T	p.Ala98Ala	synonymous_variant	Exon 2 of 13	1	NM_145201.6	ENSP00000401508.2

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

GnomAD2 exomes AF: 0.182 AC: 44532 AN: 244450 AF XY: 0.184

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 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

African (AFR) AF: 0.0959 AC: 3208 AN: 33464

American (AMR) AF: 0.213 AC: 9520 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6727 AN: 26108

East Asian (EAS) AF: 0.136 AC: 5381 AN: 39688

South Asian (SAS) AF: 0.230 AC: 19836 AN: 86234

European-Finnish (FIN) AF: 0.224 AC: 11618 AN: 51896

Middle Eastern (MID) AF: 0.237 AC: 1363 AN: 5762

European-Non Finnish (NFE) AF: 0.165 AC: 183645 AN: 1111666

Other (OTH) AF: 0.180 AC: 10872 AN: 60324

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

African (AFR) AF: 0.0940 AC: 3906 AN: 41544

American (AMR) AF: 0.182 AC: 2779 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3470

East Asian (EAS) AF: 0.113 AC: 583 AN: 5146

South Asian (SAS) AF: 0.230 AC: 1107 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2345 AN: 10604

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11206 AN: 67974

Other (OTH) AF: 0.171 AC: 361 AN: 2112

Alfa AF: 0.163 Hom.: 2229

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
PhyloP100		-0.28
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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