8-143576095-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145201.6(NAPRT):​c.1090G>A​(p.Ala364Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,450,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NAPRT
NM_145201.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0740
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.060652047).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAPRTNM_145201.6 linkuse as main transcriptc.1090G>A p.Ala364Thr missense_variant 8/13 ENST00000449291.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAPRTENST00000449291.7 linkuse as main transcriptc.1090G>A p.Ala364Thr missense_variant 8/131 NM_145201.6 P1Q6XQN6-1
ENST00000531730.1 linkuse as main transcriptn.437-566C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000483
AC:
7
AN:
1450136
Hom.:
0
Cov.:
32
AF XY:
0.00000278
AC XY:
2
AN XY:
719756
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000634
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 16, 2023The c.1090G>A (p.A364T) alteration is located in exon 8 (coding exon 8) of the NAPRT gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the alanine (A) at amino acid position 364 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Benign
0.71
DEOGEN2
Benign
0.013
T;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.52
T;.;.
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.061
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
.;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.25
N;N;N
REVEL
Benign
0.016
Sift
Benign
0.40
T;T;T
Sift4G
Benign
0.69
T;T;T
Polyphen
0.0030
B;B;B
Vest4
0.12
MutPred
0.36
Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);
MVP
0.16
MPC
0.061
ClinPred
0.055
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.044
gMVP
0.37

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: rs1824435225; hg19: chr8-144658265; COSMIC: COSV52782988; COSMIC: COSV52782988; API