dbSNP rs35975875: NAPRT:p.Arg332Cys (chr8-143576460-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145201.6(NAPRT):c.994C>T(p.Arg332Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00542 in 1,610,904 control chromosomes in the GnomAD database, including 44 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 0.0042 ( 5 hom., cov: 30)

Exomes 𝑓: 0.0055 ( 39 hom. )

Consequence

NAPRT
NM_145201.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05

Publications

10 publications found

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:

ENSG00000255050 (HGNC:):

ENSG00000255050 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052319944).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6 link	c.994C>T	p.Arg332Cys	missense_variant	Exon 7 of 13	ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7 link	c.994C>T	p.Arg332Cys	missense_variant	Exon 7 of 13	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

643

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00597

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00464

AC:

1153

AN:

248268

AF XY:

0.00490

show subpopulations

Gnomad AFR exome

AF:

0.000748

Gnomad AMR exome

AF:

0.000934

Gnomad ASJ exome

AF:

0.00555

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00649

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00554

AC:

8083

AN:

1458756

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

4135

AN XY:

725460

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

33412

American (AMR)

AF:

0.00130

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

120

AN:

26044

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39650

South Asian (SAS)

AF:

0.00465

AC:

401

AN:

86146

European-Finnish (FIN)

AF:

0.00797

AC:

416

AN:

52198

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00608

AC:

6752

AN:

1110780

Other (OTH)

AF:

0.00481

AC:

290

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

438

875

1313

1750

2188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00422

AC:

642

AN:

152148

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

298

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41500

American (AMR)

AF:

0.00170

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00353

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00481

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00597

AC:

406

AN:

67986

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00568

Hom.:

Bravo

AF:

0.00378

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00494

AC:

599

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

D;D;.

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;.;.

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Uncertain

0.071

MutationAssessor

Pathogenic

4.2

.;H;H

PhyloP100

6.0

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-7.2

D;D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.80

MVP

0.64

MPC

0.43

ClinPred

0.26

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.74

gMVP

0.89

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over