NM_002767.4:c.51A>G

Variant names:

• chr17-18865884-A-G
• rs887474957
• NM_002767.4:c.51A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002767.4(PRPSAP2):​c.51A>G​(p.Lys17Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,396,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: PRPSAP2 NM_002767.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.

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.51A>G	p.Lys17Lys	synonymous	Exon 3 of 12	NP_002758.1	O60256-1
	PRPSAP2	NM_001353098.2		c.213A>G	p.Lys71Lys	synonymous	Exon 3 of 12	NP_001340027.1
	PRPSAP2	NM_001353101.2		c.51A>G	p.Lys17Lys	synonymous	Exon 2 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.51A>G	p.Lys17Lys	synonymous	Exon 3 of 12	ENSP00000268835.2	O60256-1
	PRPSAP2	ENST00000542013.5	TSL:1	c.51A>G	p.Lys17Lys	synonymous	Exon 2 of 10	ENSP00000439129.1	O60256-3
	PRPSAP2	ENST00000610773.4	TSL:1	c.-155A>G		5_prime_UTR	Exon 3 of 11	ENSP00000481322.1	O60256-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236888 AF XY: 0.00000778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1396912 Hom.: 0 Cov.: 29 AF XY: 0.00000289 AC XY: 2 AN XY: 693202

African (AFR) AF: 0.00 AC: 0 AN: 32282

American (AMR) AF: 0.00 AC: 0 AN: 41352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24358

East Asian (EAS) AF: 0.00 AC: 0 AN: 38274

South Asian (SAS) AF: 0.00 AC: 0 AN: 75236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5510

European-Non Finnish (NFE) AF: 0.00000466 AC: 5 AN: 1072010

Other (OTH) AF: 0.00 AC: 0 AN: 57070

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		1.2
PromoterAI		0.013	Neutral

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: rs887474957; hg19: chr17-18769197;