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GeneBe

2-88691819-G-T

Variant summary

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

The NM_144563.3(RPIA):c.121G>T(p.Val41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RPIA
NM_144563.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61
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.121G>T p.Val41Leu missense_variant 1/9 ENST00000283646.5
RPIAXM_047443733.1 linkuse as main transcriptc.121G>T p.Val41Leu missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPIAENST00000283646.5 linkuse as main transcriptc.121G>T p.Val41Leu missense_variant 1/91 NM_144563.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1444834
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
717546
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:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMar 22, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RPIA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 41 of the RPIA protein (p.Val41Leu). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
0.63
D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.31
N
REVEL
Benign
0.26
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.013
D
Polyphen
0.94
P
Vest4
0.56
MutPred
0.18
Loss of sheet (P = 0.0181);
MVP
0.86
MPC
1.1
ClinPred
0.71
D
GERP RS
5.0
Varity_R
0.13
gMVP
0.30

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: rs1676937388; hg19: chr2-88991337; API