chrX-53430630-C-T

Variant names:

• chrX-53430630-C-T
• rs148562683
• NM_001031745.5:c.898C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001031745.5(RIBC1):​c.898C>T​(p.Arg300Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,203,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 144 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00040 (0 hom. 141 hem.)
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01260519).
• BS2: High Hemizygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIBC1	NM_001031745.5	MANE Select	c.898C>T	p.Arg300Cys	missense	Exon 7 of 8	NP_001026915.1	Q8N443-1
	RIBC1	NM_001267053.4		c.553C>T	p.Arg185Cys	missense	Exon 6 of 6	NP_001253982.1	Q8N443-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIBC1	ENST00000375327.6	TSL:1 MANE Select	c.898C>T	p.Arg300Cys	missense	Exon 7 of 8	ENSP00000364476.3	Q8N443-1
	RIBC1	ENST00000868183.1		c.898C>T	p.Arg300Cys	missense	Exon 7 of 8	ENSP00000538242.1
	RIBC1	ENST00000929472.1		c.898C>T	p.Arg300Cys	missense	Exon 8 of 9	ENSP00000599531.1

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 25 AN: 112137 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000285

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: 0.000394

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000457 AC: 77 AN: 168351 AF XY: 0.000436

Gnomad AFR exome AF: 0.000167

Gnomad AMR exome AF: 0.00192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000244

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000398 AC: 434 AN: 1091738 Hom.: 0 Cov.: 31 AF XY: 0.000394 AC XY: 141 AN XY: 358046

African (AFR) AF: 0.000114 AC: 3 AN: 26326

American (AMR) AF: 0.00169 AC: 58 AN: 34403

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19250

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30072

South Asian (SAS) AF: 0.0000378 AC: 2 AN: 52951

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40146

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4131

European-Non Finnish (NFE) AF: 0.000408 AC: 342 AN: 838536

Other (OTH) AF: 0.000588 AC: 27 AN: 45923

GnomAD4 genome AF: 0.000223 AC: 25 AN: 112137 Hom.: 0 Cov.: 23 AF XY: 0.0000874 AC XY: 3 AN XY: 34311

African (AFR) AF: 0.0000324 AC: 1 AN: 30855

American (AMR) AF: 0.000285 AC: 3 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3583

South Asian (SAS) AF: 0.00 AC: 0 AN: 2724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6083

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000394 AC: 21 AN: 53264

Other (OTH) AF: 0.00 AC: 0 AN: 1501

Alfa AF: 0.000194 Hom.: 8

Bravo AF: 0.000325

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.000454 AC: 55

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.16
Sift	Benign	0.058	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.54	P
Vest4		0.18
MVP		0.12
MPC		0.44
ClinPred		0.069	T
GERP RS		4.6
Varity_R		0.16
gMVP		0.49
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs148562683; hg19: chrX-53457578;