Variant 8-143578087-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000449291.7(NAPRT):c.226+6C>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,517,890 control chromosomes in the GnomAD database, including 15,805 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 0.18 ( 3418 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12387 hom. )

Consequence

NAPRT
ENST00000449291.7 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001474

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.925

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NAPRT	NM_145201.6 linkuse as main transcript	c.226+6C>A	splice_donor_region_variant, intron_variant	ENST00000449291.7	NP_660202.3
NAPRT	NM_001286829.2 linkuse as main transcript	c.226+6C>A	splice_donor_region_variant, intron_variant		NP_001273758.1
NAPRT	NM_001363145.1 linkuse as main transcript	c.226+6C>A	splice_donor_region_variant, intron_variant		NP_001350074.1
NAPRT	NM_001363146.1 linkuse as main transcript	c.-343+6C>A	splice_donor_region_variant, intron_variant		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7 linkuse as main transcript	c.226+6C>A		splice_donor_region_variant, intron_variant		1	NM_145201.6	ENSP00000401508	P1	Q6XQN6-1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27798

AN:

151630

Hom.:

3413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0996

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.182

AC:

25159

AN:

138478

Hom.:

3047

AF XY:

0.170

AC XY:

13299

AN XY:

78440

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.117

AC:

159795

AN:

1366146

Hom.:

12387

Cov.:

AF XY:

0.117

AC XY:

79155

AN XY:

673712

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0949

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.183

AC:

27835

AN:

151744

Hom.:

3418

Cov.:

AF XY:

0.184

AC XY:

13657

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0997

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.127

Hom.:

759

Bravo

AF:

0.198

Asia WGS

AF:

0.237

AC:

823

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.086

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over