rs962744633

Variant names:

• chr2-88691852-C-A
• rs962744633
• NM_144563.3:c.154C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-88691852-C-A
• chr2-88691852-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_144563.3(RPIA):​c.154C>A​(p.Arg52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPIA NM_144563.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ribose-5-P isomerase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity RPIA_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16271245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144563.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPIA	NM_144563.3	MANE Select	c.154C>A	p.Arg52Ser	missense	Exon 1 of 9	NP_653164.2	P49247

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPIA	ENST00000283646.5	TSL:1 MANE Select	c.154C>A	p.Arg52Ser	missense	Exon 1 of 9	ENSP00000283646.3	P49247
	RPIA	ENST00000871060.1		c.154C>A	p.Arg52Ser	missense	Exon 1 of 9	ENSP00000541119.1
	RPIA	ENST00000871058.1		c.154C>A	p.Arg52Ser	missense	Exon 1 of 8	ENSP00000541117.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000970 AC: 2 AN: 206270 AF XY: 0.0000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000112

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443742 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 716574

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000242 AC: 1 AN: 41390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25602

East Asian (EAS) AF: 0.00 AC: 0 AN: 39096

South Asian (SAS) AF: 0.00 AC: 0 AN: 83626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104682

Other (OTH) AF: 0.00 AC: 0 AN: 59758

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.12
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.16
Sift	Uncertain	0.016	D
Sift4G	Benign	0.69	T
Polyphen		0.023	B
Vest4		0.41
MutPred		0.38		Gain of glycosylation at R52 (P = 0.002)
MVP		0.88
MPC		0.41
ClinPred		0.20	T
GERP RS		-0.22
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.098
gMVP		0.43
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs962744633; hg19: chr2-88991370; COSMIC: COSV99376391;