X-53428082-A-C

Position:

• chrX-53428082-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000375327.6(RIBC1):​c.197A>C​(p.Tyr66Ser) variant causes a missense, splice region 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. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RIBC1 ENST00000375327.6 missense, splice_region
• Scores: Splicing: ADA: 0.00008687
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.726

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26934844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.197A>C	p.Tyr66Ser	missense_variant, splice_region_variant	4/8	ENST00000375327.6	NP_001026915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.197A>C	p.Tyr66Ser	missense_variant, splice_region_variant	4/8	1	NM_001031745.5	ENSP00000364476.3
RIBC1	ENST00000414955.6	c.197A>C	p.Tyr66Ser	missense_variant, splice_region_variant	4/6	2		ENSP00000401463.2
RIBC1	ENST00000457095.5	c.197A>C	p.Tyr66Ser	missense_variant, splice_region_variant	4/5	2		ENSP00000402080.1
RIBC1	ENST00000329209.9	c.197A>C	p.Tyr66Ser	missense_variant, splice_region_variant	4/5	3		ENSP00000332142.5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.197A>C (p.Y66S) alteration is located in exon 4 (coding exon 2) of the RIBC1 gene. This alteration results from a A to C substitution at nucleotide position 197, causing the tyrosine (Y) at amino acid position 66 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.;T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	.;M;M;M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.4	D;N;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D;T;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.81, 1.0	.;.;P;D
Vest4		0.56, 0.62
MutPred		0.63		Gain of glycosylation at Y66 (P = 0.0195);Gain of glycosylation at Y66 (P = 0.0195);Gain of glycosylation at Y66 (P = 0.0195);Gain of glycosylation at Y66 (P = 0.0195);
MVP		0.30
MPC		0.98
ClinPred		0.95	D
GERP RS		0.87
Varity_R		0.62
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.12		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.

Other links and lift over

hg19: chrX-53455030;