8-143576200-C-T

Position:

• chr8-143576200-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145201.6(NAPRT):​c.1023-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,533,766 control chromosomes in the GnomAD database, including 20,959 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.19 (3176 hom., cov: 29)
  • Exomes 𝑓: 0.15 (17783 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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]

NAPRT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.1023-38G>A		intron_variant		ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.1023-38G>A		intron_variant		1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29042 AN: 151342 Hom.: 3175 Cov.: 29

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.201 AC: 36902 AN: 183762 Hom.: 4172 AF XY: 0.194 AC XY: 19126 AN XY: 98818

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.380

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.151 AC: 208981 AN: 1382304 Hom.: 17783 Cov.: 29 AF XY: 0.151 AC XY: 102972 AN XY: 680622

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.192 AC: 29060 AN: 151462 Hom.: 3176 Cov.: 29 AF XY: 0.194 AC XY: 14366 AN XY: 73984

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.177

Alfa AF: 0.174 Hom.: 510

Bravo AF: 0.202

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.58
BranchPoint Hunter		0.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs896955; hg19: chr8-144658370; COSMIC: COSV52782717; COSMIC: COSV52782717;