rs872935

Variant names:

• chr8-143576541-G-A
• rs872935
• NM_145201.6:c.913C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143576541-G-A
• chr8-143576541-G-C

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.913C>T​(p.Leu305Leu) 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
• Publications: 29 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=-0.57).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145201.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	NM_145201.6	MANE Select	c.913C>T	p.Leu305Leu	synonymous	Exon 7 of 13	NP_660202.3
	NAPRT	NM_001286829.2		c.913C>T	p.Leu305Leu	synonymous	Exon 7 of 13	NP_001273758.1
	NAPRT	NM_001363145.1		c.913C>T	p.Leu305Leu	synonymous	Exon 7 of 12	NP_001350074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.913C>T	p.Leu305Leu	synonymous	Exon 7 of 13	ENSP00000401508.2
	NAPRT	ENST00000426292.7	TSL:1	c.913C>T	p.Leu305Leu	synonymous	Exon 7 of 13	ENSP00000390949.3
	NAPRT	ENST00000340490.7	TSL:1	n.913C>T		non_coding_transcript_exon	Exon 7 of 12	ENSP00000341136.3

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

GnomAD2 exomes AF: 0.519 AC: 128034 AN: 246698 AF XY: 0.526

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 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

African (AFR) AF: 0.215 AC: 7189 AN: 33446

American (AMR) AF: 0.457 AC: 20309 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 13319 AN: 26088

East Asian (EAS) AF: 0.377 AC: 14948 AN: 39638

South Asian (SAS) AF: 0.450 AC: 38765 AN: 86106

European-Finnish (FIN) AF: 0.528 AC: 27513 AN: 52060

Middle Eastern (MID) AF: 0.481 AC: 2769 AN: 5760

European-Non Finnish (NFE) AF: 0.630 AC: 699717 AN: 1111216

Other (OTH) AF: 0.556 AC: 33548 AN: 60290

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

African (AFR) AF: 0.229 AC: 9489 AN: 41396

American (AMR) AF: 0.550 AC: 8382 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1807 AN: 3464

East Asian (EAS) AF: 0.381 AC: 1952 AN: 5126

South Asian (SAS) AF: 0.443 AC: 2126 AN: 4804

European-Finnish (FIN) AF: 0.523 AC: 5510 AN: 10540

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.626 AC: 42504 AN: 67870

Other (OTH) AF: 0.500 AC: 1054 AN: 2106

Alfa AF: 0.549 Hom.: 16323

Bravo AF: 0.470

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.9
DANN	Benign	0.56
PhyloP100		0.21
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: rs872935; hg19: chr8-144658711; COSMIC: COSV52782682; COSMIC: COSV52782682;