rs872935

chr8-143576541-G-Achr8-143576541-G-C

Variant summary

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

The NM_145201.6(NAPRT):c.913C>T(p.Leu305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,610,826 control chromosomes in the GnomAD database, including 278,995 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 0.48 (19999 hom., cov: 31)
  • Exomes 𝑓: 0.59 (258996 hom.)
• Consequence: NAPRT NM_145201.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.57).
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.913C>T	p.Leu305=	synonymous_variant	7/13	ENST00000449291.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.913C>T	p.Leu305=	synonymous_variant	7/13	1	NM_145201.6	P1
	ENST00000531730.1	n.437-120G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73439 AN: 151636 Hom.: 19995 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.519 AC: 128034 AN: 246698 Hom.: 35004 AF XY: 0.526 AC XY: 70458 AN XY: 133926

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.379

Gnomad SAS exome AF: 0.453

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.588 AC: 858077 AN: 1459068 Hom.: 258996 Cov.: 63 AF XY: 0.585 AC XY: 424638 AN XY: 725706

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.484 AC: 73482 AN: 151758 Hom.: 19999 Cov.: 31 AF XY: 0.480 AC XY: 35577 AN XY: 74154

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.500

Alfa AF: 0.548 Hom.: 14471

Bravo AF: 0.470

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	4.9
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs872935; hg19: chr8-144658711; COSMIC: COSV52782682; COSMIC: COSV52782682;