16-29679875-C-T

Position:

• chr16-29679875-C-T

Variant summary

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

The NM_014298.6(QPRT):​c.13+665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,542 control chromosomes in the GnomAD database, including 13,220 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 0.38 (13220 hom., cov: 31)
• Consequence: QPRT NM_014298.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPRT	NM_014298.6	c.13+665C>T		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+665C>T		intron_variant		1	NM_014298.6	ENSP00000378782.4
QPRT	ENST00000449759.2	c.13+665C>T		intron_variant		3		ENSP00000404873.3
QPRT	ENST00000562473.1	c.13+665C>T		intron_variant		3		ENSP00000455183.1
QPRT	ENST00000219771.7	n.203+665C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58191 AN: 151424 Hom.: 13183 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.385 AC: 58287 AN: 151542 Hom.: 13220 Cov.: 31 AF XY: 0.388 AC XY: 28696 AN XY: 74014

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.367

Alfa AF: 0.269 Hom.: 12454

Bravo AF: 0.404

Asia WGS AF: 0.576 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.64

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: rs12596308; hg19: chr16-29691196;