Variant 17-18865884-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002767.4(PRPSAP2):c.51A>C(p.Lys17Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,549,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRPSAP2
NM_002767.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Variant links:

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]

PRPSAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33424062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPSAP2	NM_002767.4 linkuse as main transcript	c.51A>C	p.Lys17Asn	missense_variant	3/12	ENST00000268835.7	NP_002758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPSAP2	ENST00000268835.7 linkuse as main transcript	c.51A>C	p.Lys17Asn	missense_variant	3/12	1	NM_002767.4	ENSP00000268835	P1	O60256-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000484

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:

0.0000175

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

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

Dec 18, 2023

The c.51A>C (p.K17N) alteration is located in exon 3 (coding exon 1) of the PRPSAP2 gene. This alteration results from a A to C substitution at nucleotide position 51, causing the lysine (K) at amino acid position 17 to be replaced by an asparagine (N). 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

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T;.;.;.;.;.;T;T;.;T;T;.;T;.

Eigen

Benign

0.090

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.97

D;.;D;D;.;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.33

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

2.0

.;.;.;.;.;M;.;M;.;.;.;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.82

N;N;N;.;.;N;N;N;N;.;.;.;N;.;N

REVEL

Uncertain

0.40

Sift

Benign

0.15

T;D;T;.;.;T;T;D;D;.;.;.;D;.;D

Sift4G

Benign

0.34

T;T;T;T;T;T;T;T;T;D;D;T;T;D;T

Polyphen

0.61

.;.;.;.;.;.;.;P;.;.;.;.;.;.;.

Vest4

0.70, 0.64, 0.85, 0.57

MutPred

0.42

Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);Loss of ubiquitination at K17 (P = 0.0161);

MVP

0.92

MPC

1.5

ClinPred

0.74

GERP RS

4.7

Varity_R

0.21

gMVP

0.45

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