rs12678314

chr8-143577438-A-Gchr8-143577438-A-T

Variant summary

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

The NM_145201.6(NAPRT):c.438-39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,580,642 control chromosomes in the GnomAD database, including 440,218 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 0.72 (40220 hom., cov: 35)
  • Exomes 𝑓: 0.75 (399998 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.438-39T>C		intron_variant		ENST00000449291.7
NAPRT	NM_001286829.2	c.438-39T>C		intron_variant
NAPRT	NM_001363145.1	c.438-39T>C		intron_variant
NAPRT	NM_001363146.1	c.-131-39T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.438-39T>C		intron_variant		1	NM_145201.6	P1
	ENST00000531730.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110214 AN: 152044 Hom.: 40193 Cov.: 35

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.711

GnomAD3 exomes AF: 0.722 AC: 148671 AN: 205854 Hom.: 53813 AF XY: 0.718 AC XY: 81248 AN XY: 113122

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.739

Gnomad ASJ exome AF: 0.661

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.629

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.760

Gnomad OTH exome AF: 0.716

GnomAD4 exome AF: 0.747 AC: 1067151 AN: 1428480 Hom.: 399998 Cov.: 46 AF XY: 0.743 AC XY: 524967 AN XY: 706140

Gnomad4 AFR exome AF: 0.668

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.633

Gnomad4 FIN exome AF: 0.706

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.725 AC: 110300 AN: 152162 Hom.: 40220 Cov.: 35 AF XY: 0.721 AC XY: 53653 AN XY: 74382

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.712

Alfa AF: 0.690 Hom.: 4950

Bravo AF: 0.726

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.48
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: rs12678314; hg19: chr8-144659608;