8-143576200-C-T

Variant names:

• chr8-143576200-C-T
• rs896955
• NM_145201.6:c.1023-38G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	NM_145201.6	MANE Select	c.1023-38G>A		intron	N/A	NP_660202.3
	NAPRT	NM_001286829.2		c.1023-38G>A		intron	N/A	NP_001273758.1	Q6XQN6-3
	NAPRT	NM_001363145.1		c.1023-38G>A		intron	N/A	NP_001350074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.1023-38G>A		intron	N/A	ENSP00000401508.2	Q6XQN6-1
	NAPRT	ENST00000426292.7	TSL:1	c.1023-38G>A		intron	N/A	ENSP00000390949.3	Q6XQN6-3
	NAPRT	ENST00000340490.7	TSL:1	n.1023-38G>A		intron	N/A	ENSP00000341136.3	G5E977

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

GnomAD2 exomes AF: 0.201 AC: 36902 AN: 183762 AF XY: 0.194

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 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

African (AFR) AF: 0.303 AC: 9534 AN: 31448

American (AMR) AF: 0.257 AC: 9087 AN: 35296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3373 AN: 22408

East Asian (EAS) AF: 0.352 AC: 13457 AN: 38262

South Asian (SAS) AF: 0.183 AC: 14119 AN: 77330

European-Finnish (FIN) AF: 0.159 AC: 7858 AN: 49436

Middle Eastern (MID) AF: 0.178 AC: 976 AN: 5480

European-Non Finnish (NFE) AF: 0.133 AC: 141365 AN: 1065704

Other (OTH) AF: 0.162 AC: 9212 AN: 56940

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

African (AFR) AF: 0.285 AC: 11729 AN: 41180

American (AMR) AF: 0.170 AC: 2597 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1826 AN: 5082

South Asian (SAS) AF: 0.179 AC: 856 AN: 4792

European-Finnish (FIN) AF: 0.162 AC: 1710 AN: 10540

Middle Eastern (MID) AF: 0.183 AC: 53 AN: 290

European-Non Finnish (NFE) AF: 0.137 AC: 9268 AN: 67860

Other (OTH) AF: 0.177 AC: 372 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		-1.6
BranchPoint Hunter		0.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs896955; hg19: chr8-144658370; COSMIC: COSV52782717; COSMIC: COSV52782717;