16-29679583-A-G

Variant names:

• chr16-29679583-A-G
• rs9933310
• NM_014298.6:c.13+373A>G

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+373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,034 control chromosomes in the GnomAD database, including 8,358 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 0.31 (8358 hom., cov: 28)
• Consequence: QPRT NM_014298.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPRT	NM_014298.6	MANE Select	c.13+373A>G		intron	N/A	NP_055113.3
	QPRT	NM_001318249.1		c.114+373A>G		intron	N/A	NP_001305178.1
	QPRT	NM_001318250.2		c.13+373A>G		intron	N/A	NP_001305179.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPRT	ENST00000395384.9	TSL:1 MANE Select	c.13+373A>G		intron	N/A	ENSP00000378782.4
	QPRT	ENST00000449759.2	TSL:3	c.13+373A>G		intron	N/A	ENSP00000404873.3
	QPRT	ENST00000562473.1	TSL:3	c.13+373A>G		intron	N/A	ENSP00000455183.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46350 AN: 150916 Hom.: 8366 Cov.: 28

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.307 AC: 46338 AN: 151034 Hom.: 8358 Cov.: 28 AF XY: 0.311 AC XY: 22906 AN XY: 73684

African (AFR) AF: 0.106 AC: 4359 AN: 41204

American (AMR) AF: 0.349 AC: 5273 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1677 AN: 5104

South Asian (SAS) AF: 0.335 AC: 1582 AN: 4728

European-Finnish (FIN) AF: 0.415 AC: 4322 AN: 10416

Middle Eastern (MID) AF: 0.469 AC: 136 AN: 290

European-Non Finnish (NFE) AF: 0.390 AC: 26416 AN: 67726

Other (OTH) AF: 0.345 AC: 717 AN: 2078

Alfa AF: 0.358 Hom.: 6167

Bravo AF: 0.293

Asia WGS AF: 0.312 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.10
PromoterAI		-0.033	Neutral
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: rs9933310; hg19: chr16-29690904;