dbSNP rs781784358: RIBC1:p.Arg109Cys (chrX-53428408-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001031745.5(RIBC1):c.325C>T(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,208,990 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 9 hem. )

Consequence

RIBC1
NM_001031745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.595

Publications

0 publications found

Variant links:

Genes affected

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

RIBC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031745.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIBC1	NM_001031745.5	MANE Select	c.325C>T	p.Arg109Cys	missense	Exon 5 of 8	NP_001026915.1	Q8N443-1
RIBC1	NM_144968.4		c.325C>T	p.Arg109Cys	missense	Exon 5 of 5	NP_659405.1	Q8N443-2
RIBC1	NM_001267053.4		c.199+324C>T		intron	N/A	NP_001253982.1	Q8N443-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIBC1	ENST00000375327.6	TSL:1 MANE Select	c.325C>T	p.Arg109Cys	missense	Exon 5 of 8	ENSP00000364476.3	Q8N443-1
RIBC1	ENST00000868183.1		c.325C>T	p.Arg109Cys	missense	Exon 5 of 8	ENSP00000538242.1
RIBC1	ENST00000929472.1		c.325C>T	p.Arg109Cys	missense	Exon 6 of 9	ENSP00000599531.1

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000381

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

182585

AF XY:

0.0000298

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1097306

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26387

American (AMR)

AF:

0.000114

AC:

AN:

35187

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19370

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

841386

Other (OTH)

AF:

0.00

AC:

AN:

46059

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000537

AC:

AN:

111684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30667

American (AMR)

AF:

0.000381

AC:

AN:

10495

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3581

South Asian (SAS)

AF:

0.00

AC:

AN:

2678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53128

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.26

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.58

M_CAP

Benign

0.012

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-0.59

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.12

Sift

Benign

0.13

Sift4G

Benign

0.15

Polyphen

0.022

Vest4

0.075

MutPred

0.75

Loss of MoRF binding (P = 0.0068)

MVP

0.093

MPC

0.35

ClinPred

0.11

GERP RS

-2.4

Varity_R

0.18

gMVP

0.40

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.41

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over