Variant 2-210016078-C-G details in Genebe, Genetics Data Aggregator

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. 12/20 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

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]

RPE links:

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
RPE	NM_199229.3 linkuse as main transcript	c.308C>G	p.Ala103Gly	missense_variant	3/6	ENST00000359429.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPE	ENST00000359429.11 linkuse as main transcript	c.308C>G	p.Ala103Gly	missense_variant	3/6	1	NM_199229.3	P1	Q96AT9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

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:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

AN:

152140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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 submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The 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

BayesDel_noAF

Benign

-0.38

CADD

Benign

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

LIST_S2

Uncertain

0.88

D;D;.;D;.;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.81

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

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over