Genetic Variant NM_144563.3:c.84C>T (chr2-88691782-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_144563.3(RPIA):c.84C>T(p.Gly28Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,592,612 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

RPIA
NM_144563.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.12

Publications

0 publications found

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 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

RPIA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-88691782-C-T is Benign according to our data. Variant chr2-88691782-C-T is described in ClinVar as Benign. ClinVar VariationId is 742902.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.12 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00116 (176/152272) while in subpopulation AFR AF = 0.00409 (170/41562). AF 95% confidence interval is 0.00359. There are 1 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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>T	p.Gly28Gly	synonymous	Exon 1 of 9	NP_653164.2	P49247

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPIA	ENST00000283646.5	TSL:1 MANE Select	c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000283646.3	P49247
RPIA	ENST00000871060.1		c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000541119.1
RPIA	ENST00000871058.1		c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 8	ENSP00000541117.1

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000315

AC:

AN:

203230

AF XY:

0.000249

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.000227

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

184

AN:

1440340

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

715412

show subpopulations

African (AFR)

AF:

0.00455

AC:

151

AN:

33214

American (AMR)

AF:

0.000309

AC:

AN:

42072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25714

East Asian (EAS)

AF:

0.00

AC:

AN:

39272

South Asian (SAS)

AF:

0.0000236

AC:

AN:

84810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46104

Middle Eastern (MID)

AF:

0.000661

AC:

AN:

4542

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105082

Other (OTH)

AF:

0.000235

AC:

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152272

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00409

AC:

170

AN:

41562

American (AMR)

AF:

0.000327

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.00126

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.3

(source)

DANN

Benign

0.91

PhyloP100

-3.1

PromoterAI

-0.0040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over