17-76312898-C-A

Position:

• chr17-76312898-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002766.3(PRPSAP1):​c.971G>T​(p.Arg324Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPSAP1 NM_002766.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

Genes affected

PRPSAP1 (HGNC:9466): (phosphoribosyl pyrophosphate synthetase associated protein 1) Enables identical protein binding activity. Predicted to be involved in 5-phosphoribose 1-diphosphate biosynthetic process and purine nucleotide biosynthetic process. Predicted to be part of ribose phosphate diphosphokinase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPSAP1	NM_002766.3	c.971G>T	p.Arg324Leu	missense_variant	9/10	ENST00000446526.8	NP_002757.2
PRPSAP1	NM_001330503.2	c.662G>T	p.Arg221Leu	missense_variant	8/9		NP_001317432.1
PRPSAP1	NM_001366236.2	c.662G>T	p.Arg221Leu	missense_variant	9/10		NP_001353165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPSAP1	ENST00000446526.8	c.971G>T	p.Arg324Leu	missense_variant	9/10	1	NM_002766.3	ENSP00000414624.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.971G>T (p.R324L) alteration is located in exon 9 (coding exon 9) of the PRPSAP1 gene. This alteration results from a G to T substitution at nucleotide position 971, causing the arginine (R) at amino acid position 324 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	-0.065
Eigen_PC	Benign	0.076
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.64	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.018	B;.;.
Vest4		0.61
MVP		0.71
MPC		0.49
ClinPred		0.97	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.71

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: chr17-74308979;