8-143576460-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_145201.6(NAPRT):​c.994C>G​(p.Arg332Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

NAPRT
NM_145201.6 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAPRTNM_145201.6 linkc.994C>G p.Arg332Gly missense_variant Exon 7 of 13 ENST00000449291.7 NP_660202.3 Q6XQN6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAPRTENST00000449291.7 linkc.994C>G p.Arg332Gly missense_variant Exon 7 of 13 1 NM_145201.6 ENSP00000401508.2 Q6XQN6-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248268
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1458774
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
725472
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
D;D;.
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;.;.
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Uncertain
0.050
D
MutationAssessor
Pathogenic
3.7
.;H;H
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-6.3
D;D;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.84
MutPred
0.80
Loss of MoRF binding (P = 0.0261);Loss of MoRF binding (P = 0.0261);Loss of MoRF binding (P = 0.0261);
MVP
0.57
MPC
0.42
ClinPred
1.0
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.80
gMVP
0.92

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.

Other links and lift over

dbSNP: rs35975875; hg19: chr8-144658630; API