16-29679583-A-G

Position:

• chr16-29679583-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014298.6(QPRT):​c.13+373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,034 control chromosomes in the GnomAD database, including 8,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8358 hom., cov: 28)
• Consequence: QPRT NM_014298.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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]

QPRT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPRT	NM_014298.6	c.13+373A>G		intron_variant		ENST00000395384.9	NP_055113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPRT	ENST00000395384.9	c.13+373A>G		intron_variant		1	NM_014298.6	ENSP00000378782.4
QPRT	ENST00000449759.2	c.13+373A>G		intron_variant		3		ENSP00000404873.3
QPRT	ENST00000562473.1	c.13+373A>G		intron_variant		3		ENSP00000455183.1
QPRT	ENST00000219771.7	n.203+373A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46350 AN: 150916 Hom.: 8366 Cov.: 28

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46338 AN: 151034 Hom.: 8358 Cov.: 28 AF XY: 0.311 AC XY: 22906 AN XY: 73684

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.345

Alfa AF: 0.363 Hom.: 3034

Bravo AF: 0.293

Asia WGS AF: 0.312 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs9933310; hg19: chr16-29690904;