Variant X-53430649-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031745.5(RIBC1):c.917T>G(p.Leu306Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,103 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 0.0000089 ( 0 hom., 1 hem., cov: 23)

Consequence

RIBC1
NM_001031745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.470

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.072047055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RIBC1	NM_001031745.5 linkuse as main transcript	c.917T>G	p.Leu306Arg	missense_variant	7/8	ENST00000375327.6	NP_001026915.1
RIBC1	NM_001267053.4 linkuse as main transcript	c.572T>G	p.Leu191Arg	missense_variant	6/6		NP_001253982.1
RIBC1	XM_005261988.5 linkuse as main transcript	c.917T>G	p.Leu306Arg	missense_variant	7/8		XP_005262045.1
RIBC1	XM_005261990.5 linkuse as main transcript	c.572T>G	p.Leu191Arg	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.917T>G	p.Leu306Arg	missense_variant	7/8	1	NM_001031745.5	ENSP00000364476	P1	Q8N443-1
RIBC1	ENST00000414955.6 linkuse as main transcript	c.572T>G	p.Leu191Arg	missense_variant	6/6	2		ENSP00000401463		Q8N443-3

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112048

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34228

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:

0.00418

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112103

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34293

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 03, 2024

The c.917T>G (p.L306R) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a T to G substitution at nucleotide position 917, causing the leucine (L) at amino acid position 306 to be replaced by an arginine (R). 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

0.071

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.11

DANN

Benign

0.52

DEOGEN2

Benign

0.015

.;T

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.33

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.030

Sift

Benign

0.55

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.013

.;B

Vest4

0.13

MutPred

0.55

.;Loss of stability (P = 0.0156);

MVP

0.093

MPC

0.33

ClinPred

0.14

GERP RS

0.074

Varity_R

0.22

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over