NM_144563.3:c.106C>T

Variant names:

• chr2-88691804-C-T
• rs201777997
• NM_144563.3:c.106C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144563.3(RPIA):​c.106C>T​(p.Leu36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000901 in 1,442,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: RPIA NM_144563.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

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]

ACMG classification

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=0.1324743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPIA	NM_144563.3	c.106C>T	p.Leu36Phe	missense_variant	Exon 1 of 9	ENST00000283646.5	NP_653164.2
RPIA	XM_047443733.1	c.106C>T	p.Leu36Phe	missense_variant	Exon 1 of 6		XP_047299689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPIA	ENST00000283646.5	c.106C>T	p.Leu36Phe	missense_variant	Exon 1 of 9	1	NM_144563.3	ENSP00000283646.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000901 AC: 13 AN: 1442820 Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 8 AN XY: 716526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000355

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000724

Gnomad4 OTH exome AF: 0.0000335

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.22
Sift	Benign	0.084	T
Sift4G	Uncertain	0.037	D
Polyphen		0.036	B
Vest4		0.30
MutPred		0.18		Loss of sheet (P = 0.0817);
MVP		0.83
MPC		0.41
ClinPred		0.14	T
GERP RS		1.9
Varity_R		0.065
gMVP		0.16

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

Other links and lift over

dbSNP: rs201777997; hg19: chr2-88991322; COSMIC: COSV99376022;