dbSNP rs896953: NAPRT:c.226+74T>C (chr8-143578019-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_145201.6(NAPRT):c.226+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,520,020 control chromosomes in the GnomAD database, including 353,471 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 0.68 ( 34885 hom., cov: 26)

Exomes 𝑓: 0.68 ( 318586 hom. )

Consequence

NAPRT
NM_145201.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6 link	c.226+74T>C	intron_variant	Intron 1 of 12	ENST00000449291.7	NP_660202.3	Q6XQN6-1
NAPRT	NM_001286829.2 link	c.226+74T>C	intron_variant	Intron 1 of 12		NP_001273758.1	Q6XQN6-3
NAPRT	NM_001363145.1 link	c.226+74T>C	intron_variant	Intron 1 of 11		NP_001350074.1
NAPRT	NM_001363146.1 link	c.-343+74T>C	intron_variant	Intron 1 of 11		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7 link	c.226+74T>C		intron_variant	Intron 1 of 12	1	NM_145201.6	ENSP00000401508.2		Q6XQN6-1

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

102202

AN:

150124

Hom.:

34858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.675

GnomAD4 exome

AF:

0.681

AC:

933028

AN:

1369782

Hom.:

318586

Cov.:

AF XY:

0.679

AC XY:

458426

AN XY:

675188

show subpopulations

Gnomad4 AFR exome

AF:

0.660

Gnomad4 AMR exome

AF:

0.701

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.718

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.657

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.681

AC:

102283

AN:

150238

Hom.:

34885

Cov.:

AF XY:

0.679

AC XY:

49833

AN XY:

73360

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.706

Gnomad4 ASJ

AF:

0.662

Gnomad4 EAS

AF:

0.736

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.693

Gnomad4 OTH

AF:

0.677

Alfa

AF:

0.580

Hom.:

1626

Bravo

AF:

0.682

Asia WGS

AF:

0.633

AC:

2205

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.1

DANN

Benign

0.16

BranchPoint Hunter

0.0

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

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