rs549384459

Variant names:

• chr2-88691782-C-G
• rs549384459
• NM_144563.3:c.84C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-88691782-C-G
• chr2-88691782-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144563.3(RPIA):​c.84C>G​(p.Gly28Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,440,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G28G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPIA NM_144563.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.

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.84C>G	p.Gly28Gly	synonymous	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.84C>G	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000283646.3	P49247
	RPIA	ENST00000871060.1		c.84C>G	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000541119.1
	RPIA	ENST00000871058.1		c.84C>G	p.Gly28Gly	synonymous	Exon 1 of 8	ENSP00000541117.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1440340 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 715412

African (AFR) AF: 0.00 AC: 0 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 42072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25714

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.00 AC: 0 AN: 84810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4542

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105082

Other (OTH) AF: 0.00 AC: 0 AN: 59530

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.70
PhyloP100		-3.1
PromoterAI		0.053	Neutral
Mutation Taster		=98/2	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: rs549384459; hg19: chr2-88991300;