2-88691804-C-A

Position:

chr2-88691804-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144563.3(RPIA):c.106C>A(p.Leu36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,595,144 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

RPIA
NM_144563.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.664

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]

RPIA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006114602).

BP6

Variant 2-88691804-C-A is Benign according to our data. Variant chr2-88691804-C-A is described in ClinVar as [Benign]. Clinvar id is 786863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00163 (249/152324) while in subpopulation AFR AF= 0.00582 (242/41580). AF 95% confidence interval is 0.00522. There are 3 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPIA	NM_144563.3 linkuse as main transcript	c.106C>A	p.Leu36Ile	missense_variant	1/9	ENST00000283646.5	NP_653164.2	P49247
RPIA	XM_047443733.1 linkuse as main transcript	c.106C>A	p.Leu36Ile	missense_variant	1/6		XP_047299689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPIA	ENST00000283646.5 linkuse as main transcript	c.106C>A	p.Leu36Ile	missense_variant	1/9	1	NM_144563.3	ENSP00000283646.3		P49247

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00574

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000456

AC:

AN:

204150

Hom.:

AF XY:

0.000337

AC XY:

AN XY:

112662

show subpopulations

Gnomad AFR exome

AF:

0.00709

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

250

AN:

1442820

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

716526

show subpopulations

Gnomad4 AFR exome

AF:

0.00627

Gnomad4 AMR exome

AF:

0.000264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000436

GnomAD4 genome

AF:

0.00163

AC:

249

AN:

152324

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00582

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.00170

ESP6500AA

AF:

0.00447

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000499

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -

RPIA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.35

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.18

REVEL

Benign

0.15

Sift

Benign

0.26

Sift4G

Benign

0.070

Polyphen

0.0010

Vest4

0.36

MVP

0.76

MPC

0.39

ClinPred

0.015

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.062

gMVP

0.12

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