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GeneBe

2-88691841-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144563.3(RPIA):c.143A>G(p.Gln48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,599,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RPIA
NM_144563.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10988957).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPIANM_144563.3 linkuse as main transcriptc.143A>G p.Gln48Arg missense_variant 1/9 ENST00000283646.5
RPIAXM_047443733.1 linkuse as main transcriptc.143A>G p.Gln48Arg missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPIAENST00000283646.5 linkuse as main transcriptc.143A>G p.Gln48Arg missense_variant 1/91 NM_144563.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000166
AC:
24
AN:
1446974
Hom.:
0
Cov.:
32
AF XY:
0.0000167
AC XY:
12
AN XY:
718608
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:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000163
Gnomad4 OTH exome
AF:
0.0000836
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 25, 2023The c.143A>G (p.Q48R) alteration is located in exon 1 (coding exon 1) of the RPIA gene. This alteration results from a A to G substitution at nucleotide position 143, causing the glutamine (Q) at amino acid position 48 to be replaced by an arginine (R). 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
0.075
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
16
DANN
Benign
0.86
DEOGEN2
Benign
0.33
T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.0090
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.26
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.092
Sift
Benign
0.039
D
Sift4G
Benign
0.12
T
Polyphen
0.0
B
Vest4
0.31
MVP
0.63
MPC
0.39
ClinPred
0.068
T
GERP RS
1.0
Varity_R
0.050
gMVP
0.40

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: rs374258361; hg19: chr2-88991359; API