17-18898528-A-G

Variant names:

• chr17-18898528-A-G
• rs8073436
• NM_002767.4:c.584+8651A>G

Variant summary

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

The NM_002767.4(PRPSAP2):​c.584+8651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,976 control chromosomes in the GnomAD database, including 21,498 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 0.53 (21498 hom., cov: 31)
• Consequence: PRPSAP2 NM_002767.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 6 publications found

Genes affected

PRPSAP2 (HGNC:9467): (phosphoribosyl pyrophosphate synthetase associated protein 2) This gene encodes a protein that associates with the enzyme phosphoribosylpyrophosphate synthetase (PRS). PRS catalyzes the formation of phosphoribosylpyrophosphate which is a substrate for synthesis of purine and pyrimidine nucleotides, histidine, tryptophan and NAD. PRS exists as a complex with two catalytic subunits and two associated subunits. This gene encodes a non-catalytic associated subunit of PRS. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPSAP2	NM_002767.4	c.584+8651A>G		intron_variant	Intron 8 of 11	ENST00000268835.7	NP_002758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000268835.7	c.584+8651A>G		intron_variant	Intron 8 of 11	1	NM_002767.4	ENSP00000268835.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80298 AN: 151858 Hom.: 21481 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.529 AC: 80362 AN: 151976 Hom.: 21498 Cov.: 31 AF XY: 0.518 AC XY: 38497 AN XY: 74252

African (AFR) AF: 0.552 AC: 22886 AN: 41456

American (AMR) AF: 0.509 AC: 7768 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1644 AN: 5152

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4618 AN: 10538

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37728 AN: 67962

Other (OTH) AF: 0.540 AC: 1136 AN: 2102

Alfa AF: 0.448 Hom.: 1662

Bravo AF: 0.539

Asia WGS AF: 0.376 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.25
PhyloP100		-2.5
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: rs8073436; hg19: chr17-18801841;