Variant X-53426353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001031745.5(RIBC1):c.77G>A(p.Arg26Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,204,043 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000049 ( 0 hom. 21 hem. )

Consequence

RIBC1
NM_001031745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30605513).

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/8	ENST00000375327.6	NP_001026915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/8	1	NM_001031745.5	ENSP00000364476	P1	Q8N443-1
RIBC1	ENST00000414955.6 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/6	2		ENSP00000401463		Q8N443-3
RIBC1	ENST00000457095.5 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/5	2		ENSP00000402080		Q8N443-2
RIBC1	ENST00000329209.9 linkuse as main transcript	c.77G>A	p.Arg26Gln	missense_variant	3/5	3		ENSP00000332142

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111856

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34034

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000629

AC:

AN:

174858

Hom.:

AF XY:

0.0000334

AC XY:

AN XY:

59964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000485

AC:

AN:

1092131

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

357795

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.000507

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111912

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34100

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.77G>A (p.R26Q) alteration is located in exon 3 (coding exon 1) of the RIBC1 gene. This alteration results from a G to A substitution at nucleotide position 77, causing the arginine (R) at amino acid position 26 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;.;.;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

.;M;M;M

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.051

T;D;D;D

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.94, 0.87

.;.;P;P

Vest4

0.11, 0.10, 0.083

MutPred

0.80

Loss of MoRF binding (P = 0.0672);Loss of MoRF binding (P = 0.0672);Loss of MoRF binding (P = 0.0672);Loss of MoRF binding (P = 0.0672);

MVP

0.22

MPC

0.50

ClinPred

0.49

GERP RS

3.9

Varity_R

0.26

gMVP

0.88

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