17-18877717-A-T

Variant names:

• chr17-18877717-A-T
• NM_002767.4:c.259A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002767.4(PRPSAP2):​c.259A>T​(p.Met87Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPSAP2 NM_002767.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPSAP2	NM_002767.4	c.259A>T	p.Met87Leu	missense_variant	Exon 6 of 12	ENST00000268835.7	NP_002758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000268835.7	c.259A>T	p.Met87Leu	missense_variant	Exon 6 of 12	1	NM_002767.4	ENSP00000268835.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Uncertain	0.71	.;D;.;.;.;.;.;.;.;D;D;D;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.;D;D;.;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.5	.;.;.;.;.;.;.;.;.;M;.;.;.;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;D;.;D;.;.;D;D;D;D;D;.;D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0030	D;D;.;D;.;.;D;D;D;D;D;.;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.15	.;.;.;.;.;.;.;.;.;B;.;.;.;.
Vest4		0.68, 0.57, 0.71, 0.65, 0.63
MutPred		0.68		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);.;Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);.;.;Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.92
MPC		1.3
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.64
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18781030;