Variant 8-143574869-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145201.6(NAPRT):c.1586T>C(p.Val529Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,398,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NAPRT
NM_145201.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.735

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088647515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6 linkuse as main transcript	c.1586T>C	p.Val529Ala	missense_variant	13/13	ENST00000449291.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7 linkuse as main transcript	c.1586T>C	p.Val529Ala	missense_variant	13/13	1	NM_145201.6	P1	Q6XQN6-1
	ENST00000531730.1 linkuse as main transcript	n.329+74A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1398274

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689638

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:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.1586T>C (p.V529A) alteration is located in exon 13 (coding exon 13) of the NAPRT gene. This alteration results from a T to C substitution at nucleotide position 1586, causing the valine (V) at amino acid position 529 to be replaced by an alanine (A). 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

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.034

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.77

D;D;D;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.081

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.0030

B;B

Vest4

0.16

MutPred

0.39

Loss of stability (P = 0.0953);.;

MVP

0.18

MPC

0.072

ClinPred

0.30

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.45

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over