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GeneBe

2-210016078-C-G

Variant summary

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

The NM_199229.3(RPE):c.308C>G(p.Ala103Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000021 ( 0 hom. )

Consequence

RPE
NM_199229.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53
Variant links:
Genes affected
RPE (HGNC:10293): (ribulose-5-phosphate-3-epimerase) Enables metal ion binding activity; protein homodimerization activity; and ribulose-phosphate 3-epimerase activity. Involved in carbohydrate metabolic process and pentose-phosphate shunt. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24745384).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPENM_199229.3 linkuse as main transcriptc.308C>G p.Ala103Gly missense_variant 3/6 ENST00000359429.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPEENST00000359429.11 linkuse as main transcriptc.308C>G p.Ala103Gly missense_variant 3/61 NM_199229.3 P1Q96AT9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
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

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 11, 2023The c.308C>G (p.A103G) alteration is located in exon 3 (coding exon 3) of the RPE gene. This alteration results from a C to G substitution at nucleotide position 308, causing the alanine (A) at amino acid position 103 to be replaced by a glycine (G). 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
0.10
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.40
T;.;.;T;.;.;T;.;.;T;.;T;.;.;.
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D;D;.;D;.;D;D;D;D;D;D;D;.;D;D
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.78
N;N;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
0.99
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.84
N;.;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.069
Sift
Benign
0.32
T;.;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.35
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0
B;.;.;.;.;.;.;.;.;.;.;.;.;.;B
Vest4
0.38
MutPred
0.57
Loss of stability (P = 0.0838);Loss of stability (P = 0.0838);.;.;.;.;.;.;.;.;.;Loss of stability (P = 0.0838);.;.;Loss of stability (P = 0.0838);
MVP
0.37
MPC
0.27
ClinPred
0.48
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.56

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: rs2093767400; hg19: chr2-210880802; API