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2-88691804-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144563.3(RPIA):c.106C>A(p.Leu36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,595,144 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

RPIA
NM_144563.3 missense

Scores

1
17

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.664
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.006114602).
BP6
Variant 2-88691804-C-A is Benign according to our data. Variant chr2-88691804-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 786863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00163 (249/152324) while in subpopulation AFR AF= 0.00582 (242/41580). AF 95% confidence interval is 0.00522. There are 3 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPIANM_144563.3 linkuse as main transcriptc.106C>A p.Leu36Ile missense_variant 1/9 ENST00000283646.5
RPIAXM_047443733.1 linkuse as main transcriptc.106C>A p.Leu36Ile missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPIAENST00000283646.5 linkuse as main transcriptc.106C>A p.Leu36Ile missense_variant 1/91 NM_144563.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00161
AC:
245
AN:
152204
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00574
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000456
AC:
93
AN:
204150
Hom.:
0
AF XY:
0.000337
AC XY:
38
AN XY:
112662
show subpopulations
Gnomad AFR exome
AF:
0.00709
Gnomad AMR exome
AF:
0.000264
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000107
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000173
AC:
250
AN:
1442820
Hom.:
1
Cov.:
32
AF XY:
0.000133
AC XY:
95
AN XY:
716526
show subpopulations
Gnomad4 AFR exome
AF:
0.00627
Gnomad4 AMR exome
AF:
0.000264
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000474
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000436
GnomAD4 genome
AF:
0.00163
AC:
249
AN:
152324
Hom.:
3
Cov.:
33
AF XY:
0.00157
AC XY:
117
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00582
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000432
Hom.:
0
Bravo
AF:
0.00170
ESP6500AA
AF:
0.00447
AC:
16
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000499
AC:
59

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

RPIA-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 20, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
20
DANN
Benign
0.92
DEOGEN2
Benign
0.35
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.61
T
MetaRNN
Benign
0.0061
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.15
Sift
Benign
0.26
T
Sift4G
Benign
0.070
T
Polyphen
0.0010
B
Vest4
0.36
MVP
0.76
MPC
0.39
ClinPred
0.015
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.062
gMVP
0.12

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: rs201777997; hg19: chr2-88991322; API