16-29679875-C-T

Variant names:

• chr16-29679875-C-T
• rs12596308
• NM_014298.6:c.13+665C>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.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
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014298.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPRT	NM_014298.6	MANE Select	c.13+665C>T		intron	N/A	NP_055113.3
	QPRT	NM_001318249.1		c.114+665C>T		intron	N/A	NP_001305178.1	B4DDH4
	QPRT	NM_001318250.2		c.13+665C>T		intron	N/A	NP_001305179.2	H3BP73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPRT	ENST00000395384.9	TSL:1 MANE Select	c.13+665C>T		intron	N/A	ENSP00000378782.4	Q15274
	QPRT	ENST00000907275.1		c.13+665C>T		intron	N/A	ENSP00000577334.1
	QPRT	ENST00000907272.1		c.13+665C>T		intron	N/A	ENSP00000577331.1

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

African (AFR) AF: 0.610 AC: 25189 AN: 41300

American (AMR) AF: 0.400 AC: 6092 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3464

East Asian (EAS) AF: 0.600 AC: 3088 AN: 5146

South Asian (SAS) AF: 0.473 AC: 2275 AN: 4812

European-Finnish (FIN) AF: 0.279 AC: 2908 AN: 10420

Middle Eastern (MID) AF: 0.290 AC: 84 AN: 290

European-Non Finnish (NFE) AF: 0.247 AC: 16735 AN: 67874

Other (OTH) AF: 0.367 AC: 769 AN: 2094

Alfa AF: 0.294 Hom.: 33262

Bravo AF: 0.404

Asia WGS AF: 0.576 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.92
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: rs12596308; hg19: chr16-29691196;