16-29672859-T-C

Variant names:

• chr16-29672859-T-C
• rs17842268
• ENST00000449759.2:c.-78-6261T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPRT	ENST00000449759.2	c.-78-6261T>C		intron_variant	Intron 1 of 4	3		ENSP00000404873.3

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

African (AFR) AF: 0.278 AC: 11483 AN: 41286

American (AMR) AF: 0.384 AC: 5819 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3464

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5166

South Asian (SAS) AF: 0.379 AC: 1821 AN: 4810

European-Finnish (FIN) AF: 0.412 AC: 4297 AN: 10436

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26613 AN: 67880

Other (OTH) AF: 0.387 AC: 812 AN: 2098

Alfa AF: 0.377 Hom.: 14603

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
PhyloP100		-0.66

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

Other links and lift over

dbSNP: rs17842268; hg19: chr16-29684180;