chr16-29672859-T-C

Position:

• chr16-29672859-T-C

Variant summary

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

The ENST00000449759.2(QPRT):​c.-78-6261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,480 control chromosomes in the GnomAD database, including 10,212 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 0.36 (10212 hom., cov: 29)
• Consequence: QPRT ENST00000449759.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPRT	ENST00000449759.2	c.-78-6261T>C		intron_variant		3		ENSP00000404873	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54840 AN: 151362 Hom.: 10221 Cov.: 29

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.362 AC: 54843 AN: 151480 Hom.: 10212 Cov.: 29 AF XY: 0.366 AC XY: 27064 AN XY: 73990

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.387

Alfa AF: 0.389 Hom.: 1898

Bravo AF: 0.355

Asia WGS AF: 0.351 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.56

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: rs17842268; hg19: chr16-29684180;