chr16-29687304-G-T

Variant names:

• chr16-29687304-G-T
• rs9922666
• NM_014298.6:c.14-7360G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014298.6(QPRT):​c.14-7360G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,122 control chromosomes in the GnomAD database, including 6,724 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 0.29 (6724 hom., cov: 32)
• Consequence: QPRT NM_014298.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 11 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPRT	NM_014298.6	c.14-7360G>T		intron_variant	Intron 1 of 3	ENST00000395384.9	NP_055113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPRT	ENST00000395384.9	c.14-7360G>T		intron_variant	Intron 1 of 3	1	NM_014298.6	ENSP00000378782.4
QPRT	ENST00000449759.2	c.14-7360G>T		intron_variant	Intron 2 of 4	3		ENSP00000404873.3
QPRT	ENST00000562473.1	c.14-7360G>T		intron_variant	Intron 1 of 3	3		ENSP00000455183.1
QPRT	ENST00000219771.7	n.203+8094G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43623 AN: 152004 Hom.: 6705 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.287 AC: 43677 AN: 152122 Hom.: 6724 Cov.: 32 AF XY: 0.282 AC XY: 20937 AN XY: 74374

African (AFR) AF: 0.388 AC: 16107 AN: 41478

American (AMR) AF: 0.191 AC: 2911 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3470

East Asian (EAS) AF: 0.117 AC: 606 AN: 5182

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2873 AN: 10592

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18263 AN: 67994

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.271 Hom.: 15134

Bravo AF: 0.281

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.39
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs9922666; hg19: chr16-29698625;