Variant 17-76332341-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002766.3(PRPSAP1):c.385C>G(p.Pro129Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRPSAP1
NM_002766.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

Variant links:

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]

PRPSAP1 links:

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ACMG classification

Classification made for transcript

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, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPSAP1	NM_002766.3 link	c.385C>G	p.Pro129Ala	missense_variant	4/10	ENST00000446526.8	NP_002757.2	Q14558-2
PRPSAP1	NM_001330503.2 link	c.76C>G	p.Pro26Ala	missense_variant	3/9		NP_001317432.1	B4DP31
PRPSAP1	NM_001366236.2 link	c.76C>G	p.Pro26Ala	missense_variant	4/10		NP_001353165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPSAP1	ENST00000446526.8 link	c.385C>G	p.Pro129Ala	missense_variant	4/10	1	NM_002766.3	ENSP00000414624.2		Q14558-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251492

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

The c.385C>G (p.P129A) alteration is located in exon 4 (coding exon 4) of the PRPSAP1 gene. This alteration results from a C to G substitution at nucleotide position 385, causing the proline (P) at amino acid position 129 to be replaced by an alanine (A). 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

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

.;.;.;D;D;D

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D

MetaSVM

Uncertain

0.64

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.3

D;D;D;D;D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0060

D;D;D;D;D;D

Sift4G

Uncertain

0.053

T;T;D;.;.;.

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.79

MVP

0.84

MPC

1.2

ClinPred

0.97

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over