Genetic Variant PRPSAP1:p.Pro11Arg (chr17-76353672-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002766.3(PRPSAP1):c.32C>G(p.Pro11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

PRPSAP1
NM_002766.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09001309).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002766.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRPSAP1	NM_002766.3	MANE Select	c.32C>G	p.Pro11Arg	missense	Exon 1 of 10	NP_002757.2	Q14558-2
PRPSAP1	NM_001330503.2		c.-211C>G		5_prime_UTR	Exon 1 of 9	NP_001317432.1	B4DP31
PRPSAP1	NM_001366236.2		c.-140+445C>G		intron	N/A	NP_001353165.1	B4DP31

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRPSAP1	ENST00000446526.8	TSL:1 MANE Select	c.32C>G	p.Pro11Arg	missense	Exon 1 of 10	ENSP00000414624.2	Q14558-2
PRPSAP1	ENST00000908407.1		c.32C>G	p.Pro11Arg	missense	Exon 1 of 11	ENSP00000578466.1
PRPSAP1	ENST00000922958.1		c.32C>G	p.Pro11Arg	missense	Exon 1 of 10	ENSP00000593017.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.31e-7

AC:

AN:

1367304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28108

American (AMR)

AF:

0.00

AC:

AN:

33988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23912

East Asian (EAS)

AF:

0.00

AC:

AN:

32848

South Asian (SAS)

AF:

0.00

AC:

AN:

76916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4022

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070714

Other (OTH)

AF:

0.00

AC:

AN:

56880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.63

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.20

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.67

PhyloP100

1.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.50

REVEL

Benign

0.19

Sift

Benign

0.85

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.28

MutPred

0.31

Gain of MoRF binding (P = 0)

MVP

0.43

MPC

0.40

ClinPred

0.041

GERP RS

3.3

PromoterAI

-0.35

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

gMVP

0.20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over