X-53430544-C-T

Variant names:

• chrX-53430544-C-T
• rs1556894139
• NM_001031745.5:c.812C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031745.5(RIBC1):​c.812C>T​(p.Pro271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000037 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.710
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30788177).

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.812C>T	p.Pro271Leu	missense	Exon 7 of 8	NP_001026915.1	Q8N443-1
	RIBC1	NM_001267053.4		c.467C>T	p.Pro156Leu	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.812C>T	p.Pro271Leu	missense	Exon 7 of 8	ENSP00000364476.3	Q8N443-1
	RIBC1	ENST00000868183.1		c.812C>T	p.Pro271Leu	missense	Exon 7 of 8	ENSP00000538242.1
	RIBC1	ENST00000929472.1		c.812C>T	p.Pro271Leu	missense	Exon 8 of 9	ENSP00000599531.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000581 AC: 1 AN: 172131 AF XY: 0.0000172

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000365 AC: 4 AN: 1094561 Hom.: 0 Cov.: 31 AF XY: 0.00000833 AC XY: 3 AN XY: 360215

African (AFR) AF: 0.00 AC: 0 AN: 26343

American (AMR) AF: 0.00 AC: 0 AN: 34705

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19321

East Asian (EAS) AF: 0.00 AC: 0 AN: 30087

South Asian (SAS) AF: 0.0000747 AC: 4 AN: 53538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840174

Other (OTH) AF: 0.00 AC: 0 AN: 45967

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.20
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.71
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.67		Loss of disorder (P = 0.0404)
MVP		0.24
MPC		0.37
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.52
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1556894139; hg19: chrX-53457492;