Variant X-53428405-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001031745.5(RIBC1):c.322G>A(p.Gly108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,209,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.000027 ( 0 hom. 8 hem. )

Consequence

RIBC1
NM_001031745.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0820

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051359534).

BP6

Variant X-53428405-G-A is Benign according to our data. Variant chrX-53428405-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2397499.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5 linkuse as main transcript	c.322G>A	p.Gly108Arg	missense_variant	5/8	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.322G>A	p.Gly108Arg	missense_variant	5/8	1	NM_001031745.5	ENSP00000364476	P1	Q8N443-1
RIBC1	ENST00000457095.5 linkuse as main transcript	c.322G>A	p.Gly108Arg	missense_variant	5/5	2		ENSP00000402080		Q8N443-2
RIBC1	ENST00000329209.9 linkuse as main transcript	c.322G>A	p.Gly108Arg	missense_variant	5/5	3		ENSP00000332142
RIBC1	ENST00000414955.6 linkuse as main transcript	c.199+321G>A		intron_variant		2		ENSP00000401463		Q8N443-3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

111787

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

33969

show subpopulations

Gnomad AFR

AF:

0.000716

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:

0.0000766

AC:

AN:

182653

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67123

show subpopulations

Gnomad AFR exome

AF:

0.000994

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1097522

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

362894

show subpopulations

Gnomad4 AFR exome

AF:

0.000910

Gnomad4 AMR exome

AF:

0.00

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:

0.00000356

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000197

AC:

AN:

111841

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34033

show subpopulations

Gnomad4 AFR

AF:

0.000715

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

Bravo

AF:

0.000249

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.79

DANN

Benign

0.79

DEOGEN2

Benign

0.025

T;.;T

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

4.6

N;N;N

REVEL

Benign

0.091

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0, 0.0030

.;B;B

Vest4

0.059, 0.024

MutPred

0.57

Gain of MoRF binding (P = 0.0222);Gain of MoRF binding (P = 0.0222);Gain of MoRF binding (P = 0.0222);

MVP

0.068

MPC

0.26

ClinPred

0.019

GERP RS

-0.039

Varity_R

0.066

gMVP

0.083

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