17-18850557-C-T

Position:

• chr17-18850557-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441887.5(PRPSAP2):​c.-33+8193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,038 control chromosomes in the GnomAD database, including 41,187 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 0.73 (41187 hom., cov: 31)
• Consequence: PRPSAP2 ENST00000441887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.18850557C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000441887.5	c.-33+8193C>T		intron_variant		5		ENSP00000395127.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111414 AN: 151920 Hom.: 41133 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.734 AC: 111528 AN: 152038 Hom.: 41187 Cov.: 31 AF XY: 0.732 AC XY: 54336 AN XY: 74278

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.734

Alfa AF: 0.703 Hom.: 86084

Bravo AF: 0.748

Asia WGS AF: 0.744 AC: 2589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4924935; hg19: chr17-18753870;