Variant X-53430617-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000375327.6(RIBC1):c.885G>C(p.Lys295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,204,535 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000049 ( 0 hom. 17 hem. )

Consequence

RIBC1
ENST00000375327.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15988848).

BS2

High Hemizygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5 linkuse as main transcript	c.885G>C	p.Lys295Asn	missense_variant	7/8	ENST00000375327.6	NP_001026915.1	Q8N443-1A0A024R9X7
RIBC1	NM_001267053.4 linkuse as main transcript	c.540G>C	p.Lys180Asn	missense_variant	6/6		NP_001253982.1	Q8N443-3
RIBC1	XM_005261988.5 linkuse as main transcript	c.885G>C	p.Lys295Asn	missense_variant	7/8		XP_005262045.1	Q8N443-1A0A024R9X7
RIBC1	XM_005261990.5 linkuse as main transcript	c.540G>C	p.Lys180Asn	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.885G>C	p.Lys295Asn	missense_variant	7/8	1	NM_001031745.5	ENSP00000364476.3		Q8N443-1
RIBC1	ENST00000414955.6 linkuse as main transcript	c.540G>C	p.Lys180Asn	missense_variant	6/6	2		ENSP00000401463.2		Q8N443-3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34498

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000562

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

168528

Hom.:

AF XY:

0.0000181

AC XY:

AN XY:

55102

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000485

AC:

AN:

1092169

Hom.:

Cov.:

AF XY:

0.0000474

AC XY:

AN XY:

358361

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

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:

0.0000596

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34498

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000562

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

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 22, 2021

The c.885G>C (p.K295N) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a G to C substitution at nucleotide position 885, causing the lysine (K) at amino acid position 295 to be replaced by an asparagine (N). 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

0.22

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

.;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.36

.;B

Vest4

0.17

MutPred

0.49

.;Loss of glycosylation at K295 (P = 0.0878);

MVP

0.20

MPC

0.30

ClinPred

0.18

GERP RS

-0.26

Varity_R

0.26

gMVP

0.33

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