Variant 8-143574982-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145201.6(NAPRT):c.1554+4G>C 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 0.0757 in 1,542,460 control chromosomes in the GnomAD database, including 4,888 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 0.076 ( 475 hom., cov: 34)

Exomes 𝑓: 0.076 ( 4413 hom. )

Consequence

NAPRT
NM_145201.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.004719

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

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:

(HGNC:):

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAPRT	NM_145201.6 linkuse as main transcript	c.1554+4G>C		splice_donor_region_variant, intron_variant		ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7 linkuse as main transcript	c.1554+4G>C		splice_donor_region_variant, intron_variant		1	NM_145201.6	ENSP00000401508	P1	Q6XQN6-1
	ENST00000531730.1 linkuse as main transcript	n.330-18C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11517

AN:

152164

Hom.:

475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0799

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0686

Gnomad OTH

AF:

0.0699

GnomAD3 exomes

AF:

0.0823

AC:

12015

AN:

146016

Hom.:

580

AF XY:

0.0868

AC XY:

6714

AN XY:

77312

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0668

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0735

Gnomad NFE exome

AF:

0.0710

Gnomad OTH exome

AF:

0.0860

GnomAD4 exome

AF:

0.0757

AC:

105236

AN:

1390178

Hom.:

4413

Cov.:

AF XY:

0.0775

AC XY:

53058

AN XY:

684924

show subpopulations

Gnomad4 AFR exome

AF:

0.0800

Gnomad4 AMR exome

AF:

0.0438

Gnomad4 ASJ exome

AF:

0.0643

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0689

Gnomad4 NFE exome

AF:

0.0704

Gnomad4 OTH exome

AF:

0.0790

GnomAD4 genome

AF:

0.0757

AC:

11523

AN:

152282

Hom.:

475

Cov.:

AF XY:

0.0763

AC XY:

5680

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0799

Gnomad4 AMR

AF:

0.0558

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0686

Gnomad4 OTH

AF:

0.0701

Alfa

AF:

0.0469

Hom.:

Bravo

AF:

0.0734

Asia WGS

AF:

0.167

AC:

578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.0

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0047

dbscSNV1_RF

Benign

0.11

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