chr17-18928832-G-A

Variant names:

• chr17-18928832-G-A
• NM_002767.4:c.826G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002767.4(PRPSAP2):​c.826G>A​(p.Asp276Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D276G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPSAP2 NM_002767.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3785336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002767.4. 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
	PRPSAP2	NM_002767.4	MANE Select	c.826G>A	p.Asp276Asn	missense	Exon 11 of 12	NP_002758.1	O60256-1
	PRPSAP2	NM_001353098.2		c.988G>A	p.Asp330Asn	missense	Exon 11 of 12	NP_001340027.1
	PRPSAP2	NM_001353101.2		c.826G>A	p.Asp276Asn	missense	Exon 10 of 11	NP_001340030.1	O60256-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP2	ENST00000268835.7	TSL:1 MANE Select	c.826G>A	p.Asp276Asn	missense	Exon 11 of 12	ENSP00000268835.2	O60256-1
	PRPSAP2	ENST00000610773.4	TSL:1	c.568G>A	p.Asp190Asn	missense	Exon 10 of 11	ENSP00000481322.1	O60256-4
	PRPSAP2	ENST00000542013.5	TSL:1	c.805-1708G>A		intron	N/A	ENSP00000439129.1	O60256-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
PhyloP100		7.9
Varity_R		0.21
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-18832145;