8-143577438-A-G

Variant names:

• chr8-143577438-A-G
• rs12678314
• NM_145201.6:c.438-39T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 -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.

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.438-39T>C		intron	N/A	NP_660202.3
	NAPRT	NM_001286829.2		c.438-39T>C		intron	N/A	NP_001273758.1
	NAPRT	NM_001363145.1		c.438-39T>C		intron	N/A	NP_001350074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.438-39T>C		intron	N/A	ENSP00000401508.2
	NAPRT	ENST00000426292.7	TSL:1	c.438-39T>C		intron	N/A	ENSP00000390949.3
	NAPRT	ENST00000340490.7	TSL:1	n.438-39T>C		intron	N/A	ENSP00000341136.3

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

GnomAD2 exomes AF: 0.722 AC: 148671 AN: 205854 AF XY: 0.718

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 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

African (AFR) AF: 0.668 AC: 22033 AN: 32978

American (AMR) AF: 0.735 AC: 30201 AN: 41070

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 16868 AN: 25338

East Asian (EAS) AF: 0.717 AC: 27700 AN: 38634

South Asian (SAS) AF: 0.633 AC: 52620 AN: 83082

European-Finnish (FIN) AF: 0.706 AC: 35070 AN: 49664

Middle Eastern (MID) AF: 0.690 AC: 2972 AN: 4310

European-Non Finnish (NFE) AF: 0.764 AC: 836707 AN: 1094546

Other (OTH) AF: 0.730 AC: 42980 AN: 58858

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

African (AFR) AF: 0.671 AC: 27841 AN: 41508

American (AMR) AF: 0.744 AC: 11381 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2323 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3796 AN: 5172

South Asian (SAS) AF: 0.620 AC: 2994 AN: 4826

European-Finnish (FIN) AF: 0.709 AC: 7520 AN: 10604

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52073 AN: 67962

Other (OTH) AF: 0.712 AC: 1504 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.76
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: rs12678314; hg19: chr8-144659608;