rs1737947

Variant names:

• chr17-18928119-A-G
• rs1737947
• NM_002767.4:c.805-692A>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.805-692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 153,224 control chromosomes in the GnomAD database, including 5,885 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 0.27 (5815 hom., cov: 31)
  • Exomes 𝑓: 0.28 (70 hom.)
• Consequence: PRPSAP2 NM_002767.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP2	NM_002767.4	MANE Select	c.805-692A>G		intron	N/A	NP_002758.1
	PRPSAP2	NM_001353098.2		c.967-692A>G		intron	N/A	NP_001340027.1
	PRPSAP2	NM_001353101.2		c.805-692A>G		intron	N/A	NP_001340030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPSAP2	ENST00000268835.7	TSL:1 MANE Select	c.805-692A>G		intron	N/A	ENSP00000268835.2
	PRPSAP2	ENST00000542013.5	TSL:1	c.805-2421A>G		intron	N/A	ENSP00000439129.1
	PRPSAP2	ENST00000610773.4	TSL:1	c.547-692A>G		intron	N/A	ENSP00000481322.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41373 AN: 151776 Hom.: 5813 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.275 AC: 366 AN: 1330 Hom.: 70 AF XY: 0.251 AC XY: 177 AN XY: 704

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.144 AC: 30 AN: 208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.154 AC: 4 AN: 26

South Asian (SAS) AF: 0.338 AC: 27 AN: 80

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.302 AC: 289 AN: 958

Other (OTH) AF: 0.240 AC: 12 AN: 50

GnomAD4 genome AF: 0.272 AC: 41383 AN: 151894 Hom.: 5815 Cov.: 31 AF XY: 0.274 AC XY: 20337 AN XY: 74240

African (AFR) AF: 0.222 AC: 9172 AN: 41380

American (AMR) AF: 0.236 AC: 3595 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3468

East Asian (EAS) AF: 0.144 AC: 747 AN: 5176

South Asian (SAS) AF: 0.401 AC: 1929 AN: 4812

European-Finnish (FIN) AF: 0.302 AC: 3181 AN: 10550

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20917 AN: 67938

Other (OTH) AF: 0.276 AC: 582 AN: 2110

Alfa AF: 0.302 Hom.: 3732

Bravo AF: 0.260

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.42
PhyloP100		-1.4
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: rs1737947; hg19: chr17-18831432;