rs744650

Positions:

• chr8-143576560-G-A

Variant summary

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

The ENST00000449291.7(NAPRT):​c.894C>T​(p.Pro298=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,610,952 control chromosomes in the GnomAD database, including 596 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 0.021 (57 hom., cov: 33)
  • Exomes 𝑓: 0.024 (539 hom.)
• Consequence: NAPRT ENST00000449291.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.03 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.894C>T	p.Pro298=	synonymous_variant	7/13	ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.894C>T	p.Pro298=	synonymous_variant	7/13	1	NM_145201.6	ENSP00000401508	P1
	ENST00000531730.1	n.437-101G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3211 AN: 152050 Hom.: 57 Cov.: 33

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0253 AC: 6234 AN: 246460 Hom.: 120 AF XY: 0.0258 AC XY: 3451 AN XY: 133922

Gnomad AFR exome AF: 0.00467

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0189

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0331

GnomAD4 exome AF: 0.0243 AC: 35413 AN: 1458784 Hom.: 539 Cov.: 36 AF XY: 0.0245 AC XY: 17748 AN XY: 725612

Gnomad4 AFR exome AF: 0.00317

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.0558

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.0211 AC: 3208 AN: 152168 Hom.: 57 Cov.: 33 AF XY: 0.0233 AC XY: 1735 AN XY: 74400

Gnomad4 AFR AF: 0.00424

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0225 Hom.: 43

Bravo AF: 0.0155

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.5
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs744650; hg19: chr8-144658730;