rs744650

Variant names:

• chr8-143576560-G-A
• rs744650
• NM_145201.6:c.894C>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.894C>T​(p.Pro298Pro) 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 NM_145201.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 5 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=-0.52).
• 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.

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.894C>T	p.Pro298Pro	synonymous	Exon 7 of 13	NP_660202.3
	NAPRT	NM_001286829.2		c.894C>T	p.Pro298Pro	synonymous	Exon 7 of 13	NP_001273758.1
	NAPRT	NM_001363145.1		c.894C>T	p.Pro298Pro	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.894C>T	p.Pro298Pro	synonymous	Exon 7 of 13	ENSP00000401508.2
	NAPRT	ENST00000426292.7	TSL:1	c.894C>T	p.Pro298Pro	synonymous	Exon 7 of 13	ENSP00000390949.3
	NAPRT	ENST00000340490.7	TSL:1	n.894C>T		non_coding_transcript_exon	Exon 7 of 12	ENSP00000341136.3

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

GnomAD2 exomes AF: 0.0253 AC: 6234 AN: 246460 AF XY: 0.0258

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 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

African (AFR) AF: 0.00317 AC: 106 AN: 33440

American (AMR) AF: 0.0139 AC: 619 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.0558 AC: 1449 AN: 25990

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39660

South Asian (SAS) AF: 0.0199 AC: 1715 AN: 86046

European-Finnish (FIN) AF: 0.0724 AC: 3763 AN: 51974

Middle Eastern (MID) AF: 0.0556 AC: 320 AN: 5754

European-Non Finnish (NFE) AF: 0.0233 AC: 25868 AN: 1111130

Other (OTH) AF: 0.0260 AC: 1566 AN: 60290

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

African (AFR) AF: 0.00424 AC: 176 AN: 41520

American (AMR) AF: 0.0144 AC: 221 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4826

European-Finnish (FIN) AF: 0.0785 AC: 832 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0242 AC: 1642 AN: 67984

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0224 Hom.: 49

Bravo AF: 0.0155

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		0.030
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs744650; hg19: chr8-144658730;