rs745444576

Variant names:

• chr16-29694775-C-A
• rs745444576
• NM_014298.6:c.125C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-29694775-C-A
• chr16-29694775-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014298.6(QPRT):​c.125C>A​(p.Ser42*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: QPRT NM_014298.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

QPRT (HGNC:9755): (quinolinate phosphoribosyltransferase) This gene encodes a key enzyme in catabolism of quinolinate, an intermediate in the tryptophan-nicotinamide adenine dinucleotide pathway. Quinolinate acts as a most potent endogenous exitotoxin to neurons. Elevation of quinolinate levels in the brain has been linked to the pathogenesis of neurodegenerative disorders such as epilepsy, Alzheimer's disease, and Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPRT	NM_014298.6	c.125C>A	p.Ser42*	stop_gained	Exon 2 of 4	ENST00000395384.9	NP_055113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPRT	ENST00000395384.9	c.125C>A	p.Ser42*	stop_gained	Exon 2 of 4	1	NM_014298.6	ENSP00000378782.4
QPRT	ENST00000449759.2	c.125C>A	p.Ser42*	stop_gained	Exon 3 of 5	3		ENSP00000404873.3
QPRT	ENST00000562473.1	c.105+20C>A		intron_variant	Intron 2 of 3	3		ENSP00000455183.1
QPRT	ENST00000219771.7	n.204-2221C>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.020	N
PhyloP100		1.1
Vest4		0.79
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs745444576; hg19: chr16-29706096;