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GeneBe

2-88691753-C-A

Variant summary

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

The NM_144563.3(RPIA):c.55C>A(p.Pro19Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P19P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RPIA
NM_144563.3 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64
Variant links:
Genes affected
RPIA (HGNC:10297): (ribose 5-phosphate isomerase A) The protein encoded by this gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway. This gene is highly conserved in most organisms. The enzyme plays an essential role in the carbohydrate metabolism. Mutations in this gene cause ribose 5-phosphate isomerase deficiency. A pseudogene is found on chromosome 18. [provided by RefSeq, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
RPIANM_144563.3 linkuse as main transcriptc.55C>A p.Pro19Thr missense_variant 1/9 ENST00000283646.5
RPIAXM_047443733.1 linkuse as main transcriptc.55C>A p.Pro19Thr missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPIAENST00000283646.5 linkuse as main transcriptc.55C>A p.Pro19Thr missense_variant 1/91 NM_144563.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000473
AC:
1
AN:
211294
Hom.:
0
AF XY:
0.00000851
AC XY:
1
AN XY:
117538
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000109
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.93e-7
AC:
1
AN:
1442690
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
717218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000873
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Deficiency of ribose-5-phosphate isomerase Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.51
D
MetaSVM
Uncertain
-0.047
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.88
D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.99
N
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.23
Gain of phosphorylation at P19 (P = 0.029);
MVP
0.89
MPC
1.0
ClinPred
0.96
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.45
gMVP
0.39

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.

Other links and lift over

dbSNP: rs756750653; hg19: chr2-88991271; API