Genetic Variant RIBC1:p.Arg300Cys (chrX-53430630-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001031745.5(RIBC1):c.898C>T(p.Arg300Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,203,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 144 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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: 𝑓 0.00022 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 0 hom. 141 hem. )

Consequence

RIBC1
NM_001031745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Variant links:

Genes affected

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

RIBC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01260519).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIBC1	NM_001031745.5 link	c.898C>T	p.Arg300Cys	missense_variant	Exon 7 of 8	ENST00000375327.6	NP_001026915.1	Q8N443-1A0A024R9X7
RIBC1	NM_001267053.4 link	c.553C>T	p.Arg185Cys	missense_variant	Exon 6 of 6		NP_001253982.1	Q8N443-3
RIBC1	XM_005261988.5 link	c.898C>T	p.Arg300Cys	missense_variant	Exon 7 of 8		XP_005262045.1	Q8N443-1A0A024R9X7
RIBC1	XM_005261990.5 link	c.553C>T	p.Arg185Cys	missense_variant	Exon 6 of 7		XP_005262047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6 link	c.898C>T	p.Arg300Cys	missense_variant	Exon 7 of 8	1	NM_001031745.5	ENSP00000364476.3		Q8N443-1
RIBC1	ENST00000414955.6 link	c.553C>T	p.Arg185Cys	missense_variant	Exon 6 of 6	2		ENSP00000401463.2		Q8N443-3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

112137

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34311

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

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:

0.000394

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000457

AC:

AN:

168351

Hom.:

AF XY:

0.000436

AC XY:

AN XY:

55041

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000398

AC:

434

AN:

1091738

Hom.:

Cov.:

AF XY:

0.000394

AC XY:

141

AN XY:

358046

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00169

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000408

Gnomad4 OTH exome

AF:

0.000588

GnomAD4 genome

AF:

0.000223

AC:

AN:

112137

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34311

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000394

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000454

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.898C>T (p.R300C) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a C to T substitution at nucleotide position 898, causing the arginine (R) at amino acid position 300 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;T

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

.;L

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.16

Sift

Benign

0.058

T;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.54

.;P

Vest4

0.18

MVP

0.12

MPC

0.44

ClinPred

0.069

GERP RS

4.6

Varity_R

0.16

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over