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GeneBe

2-88691714-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_144563.3(RPIA):c.16C>T(p.Pro6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000925 in 1,577,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

RPIA
NM_144563.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000131 (20/152356) while in subpopulation AFR AF= 0.000168 (7/41584). AF 95% confidence interval is 0.0000905. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPIANM_144563.3 linkuse as main transcriptc.16C>T p.Pro6Ser missense_variant 1/9 ENST00000283646.5
RPIAXM_047443733.1 linkuse as main transcriptc.16C>T p.Pro6Ser missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPIAENST00000283646.5 linkuse as main transcriptc.16C>T p.Pro6Ser missense_variant 1/91 NM_144563.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000533
AC:
11
AN:
206358
Hom.:
0
AF XY:
0.0000608
AC XY:
7
AN XY:
115194
show subpopulations
Gnomad AFR exome
AF:
0.000157
Gnomad AMR exome
AF:
0.0000326
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:
0.0000860
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000884
AC:
126
AN:
1425444
Hom.:
0
Cov.:
32
AF XY:
0.0000933
AC XY:
66
AN XY:
707576
show subpopulations
Gnomad4 AFR exome
AF:
0.0000618
Gnomad4 AMR exome
AF:
0.0000243
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000119
Gnomad4 NFE exome
AF:
0.000105
Gnomad4 OTH exome
AF:
0.0000511
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152356
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000126
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000552
AC:
4
ExAC
AF:
0.0000343
AC:
4

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 GeneticsMar 06, 2023The c.16C>T (p.P6S) alteration is located in exon 1 (coding exon 1) of the RPIA gene. This alteration results from a C to T substitution at nucleotide position 16, causing the proline (P) at amino acid position 6 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.0046
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.75
T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Uncertain
-0.079
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.88
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.40
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.59
MVP
0.89
MPC
0.37
ClinPred
0.26
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.40
gMVP
0.34

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: rs368598511; hg19: chr2-88991232; API