8-143575648-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145201.6(NAPRT):​c.1162C>G​(p.Gln388Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NAPRT
NM_145201.6 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAPRTNM_145201.6 linkuse as main transcriptc.1162C>G p.Gln388Glu missense_variant 9/13 ENST00000449291.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAPRTENST00000449291.7 linkuse as main transcriptc.1162C>G p.Gln388Glu missense_variant 9/131 NM_145201.6 P1Q6XQN6-1
ENST00000531730.1 linkuse as main transcriptn.436+542G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
32

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 GeneticsOct 26, 2022The c.1162C>G (p.Q388E) alteration is located in exon 9 (coding exon 9) of the NAPRT gene. This alteration results from a C to G substitution at nucleotide position 1162, causing the glutamine (Q) at amino acid position 388 to be replaced by a glutamic acid (E). 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
0.26
BayesDel_addAF
Benign
-0.0052
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.075
T;T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.95
D;.;.
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.6
.;L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Benign
0.28
Sift
Uncertain
0.0010
D;D;D
Sift4G
Benign
0.099
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.59
MutPred
0.68
Loss of catalytic residue at Q388 (P = 0.1187);Loss of catalytic residue at Q388 (P = 0.1187);Loss of catalytic residue at Q388 (P = 0.1187);
MVP
0.41
MPC
0.38
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.56
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-144657818; API