chr2-88691819-G-T

Variant names:

• chr2-88691819-G-T
• rs1676937388
• NM_144563.3:c.121G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144563.3(RPIA):​c.121G>T​(p.Val41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPIA NM_144563.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• 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.

• PM2: Very rare variant in population databases, with high coverage

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.121G>T	p.Val41Leu	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.121G>T	p.Val41Leu	missense	Exon 1 of 9	ENSP00000283646.3	P49247
	RPIA	ENST00000871060.1		c.121G>T	p.Val41Leu	missense	Exon 1 of 9	ENSP00000541119.1
	RPIA	ENST00000871058.1		c.121G>T	p.Val41Leu	missense	Exon 1 of 8	ENSP00000541117.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444834 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717546

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 41770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 84232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5348

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105712

Other (OTH) AF: 0.00 AC: 0 AN: 59740

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.94	P
Vest4		0.56
MutPred		0.18		Loss of sheet (P = 0.0181)
MVP		0.86
MPC		1.1
ClinPred		0.71	D
GERP RS		5.0
PromoterAI		0.45	Neutral
Varity_R		0.13
gMVP		0.30
Mutation Taster		=89/11	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: rs1676937388; hg19: chr2-88991337;