Variant X-53430633-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000375327.6(RIBC1):c.901C>G(p.Gln301Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,204,481 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 0 hem. )

Consequence

RIBC1
ENST00000375327.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06753197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5 linkuse as main transcript	c.901C>G	p.Gln301Glu	missense_variant	7/8	ENST00000375327.6	NP_001026915.1	Q8N443-1A0A024R9X7
RIBC1	NM_001267053.4 linkuse as main transcript	c.556C>G	p.Gln186Glu	missense_variant	6/6		NP_001253982.1	Q8N443-3
RIBC1	XM_005261988.5 linkuse as main transcript	c.901C>G	p.Gln301Glu	missense_variant	7/8		XP_005262045.1	Q8N443-1A0A024R9X7
RIBC1	XM_005261990.5 linkuse as main transcript	c.556C>G	p.Gln186Glu	missense_variant	6/7		XP_005262047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6 linkuse as main transcript	c.901C>G	p.Gln301Glu	missense_variant	7/8	1	NM_001031745.5	ENSP00000364476.3		Q8N443-1
RIBC1	ENST00000414955.6 linkuse as main transcript	c.556C>G	p.Gln186Glu	missense_variant	6/6	2		ENSP00000401463.2		Q8N443-3

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112303

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34467

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000593

AC:

AN:

168694

Hom.:

AF XY:

0.00

AC XY:

AN XY:

55292

show subpopulations

Gnomad AFR exome

AF:

0.0000834

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000732

AC:

AN:

1092178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358436

show subpopulations

Gnomad4 AFR exome

AF:

0.000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112303

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34467

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000825

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

Jun 02, 2023

The c.901C>G (p.Q301E) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a C to G substitution at nucleotide position 901, causing the glutamine (Q) at amino acid position 301 to be replaced by a glutamic acid (E). 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

0.075

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.46

DANN

Benign

0.46

DEOGEN2

Benign

0.015

.;T

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.87

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.064

Sift

Benign

0.58

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.097

.;B

Vest4

0.095

MVP

0.18

MPC

0.25

ClinPred

0.11

GERP RS

1.6

Varity_R

0.091

gMVP

0.13

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