chr8-143576550-C-T

Position:

• chr8-143576550-C-T

Variant summary

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

The NM_145201.6(NAPRT):​c.904G>A​(p.Ala302Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NAPRT NM_145201.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30

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]

(HGNC:):

ACMG classification

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
NAPRT	NM_145201.6	c.904G>A	p.Ala302Thr	missense_variant	7/13	ENST00000449291.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.904G>A	p.Ala302Thr	missense_variant	7/13	1	NM_145201.6	P1
	ENST00000531730.1	n.437-111C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459416 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 725952

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.904G>A (p.A302T) alteration is located in exon 7 (coding exon 7) of the NAPRT gene. This alteration results from a G to A substitution at nucleotide position 904, causing the alanine (A) at amino acid position 302 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	0.24
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;.;.
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.6	.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.51
MutPred		0.48		Loss of stability (P = 0.2725);Loss of stability (P = 0.2725);Loss of stability (P = 0.2725);
MVP		0.37
MPC		0.37
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.59
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1035749950; hg19: chr8-144658720;