Variant X-53428046-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000375327.6(RIBC1):c.161G>A(p.Arg54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,097,880 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000014 ( 0 hom. 4 hem. )

Consequence

RIBC1
ENST00000375327.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

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=0.039659083).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	4/8	ENST00000375327.6	NP_001026915.1	Q8N443-1A0A024R9X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIBC1	ENST00000375327.6 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	4/8	1	NM_001031745.5	ENSP00000364476.3	Q8N443-1
RIBC1	ENST00000414955.6 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	4/6	2		ENSP00000401463.2	Q8N443-3
RIBC1	ENST00000457095.5 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	4/5	2		ENSP00000402080.1	Q8N443-2
RIBC1	ENST00000329209.9 linkuse as main transcript	c.161G>A	p.Arg54His	missense_variant	4/5	3		ENSP00000332142.5	A0A0C4DFR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

182982

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000527

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1097880

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

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

Sep 14, 2022

The c.161G>A (p.R54H) alteration is located in exon 4 (coding exon 2) of the RIBC1 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a histidine (H). 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

0.086

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.0

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;.;.;T

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.53

T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.75

.;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.033

D;T;D;D

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.20, 0.19

.;.;B;B

Vest4

0.032, 0.033, 0.020

MVP

0.068

MPC

0.27

ClinPred

0.0061

GERP RS

-0.84

Varity_R

0.091

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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