X-53428058-C-T

Variant names:

• chrX-53428058-C-T
• NM_001031745.5:c.173C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031745.5(RIBC1):​c.173C>T​(p.Ala58Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.816

Genes affected

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

ACMG classification

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=0.08843264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.173C>T	p.Ala58Val	missense_variant	Exon 4 of 8	ENST00000375327.6	NP_001026915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.173C>T	p.Ala58Val	missense_variant	Exon 4 of 8	1	NM_001031745.5	ENSP00000364476.3
RIBC1	ENST00000414955.6	c.173C>T	p.Ala58Val	missense_variant	Exon 4 of 6	2		ENSP00000401463.2
RIBC1	ENST00000457095.5	c.173C>T	p.Ala58Val	missense_variant	Exon 4 of 5	2		ENSP00000402080.1
RIBC1	ENST00000329209.9	c.173C>T	p.Ala58Val	missense_variant	Exon 4 of 5	3		ENSP00000332142.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173C>T (p.A58V) alteration is located in exon 4 (coding exon 2) of the RIBC1 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the alanine (A) at amino acid position 58 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T;.;.;T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.60	N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.021, 0.27	.;.;B;B
Vest4		0.052, 0.049, 0.044
MutPred		0.45		Gain of methylation at K62 (P = 0.0882);Gain of methylation at K62 (P = 0.0882);Gain of methylation at K62 (P = 0.0882);Gain of methylation at K62 (P = 0.0882);
MVP		0.10
MPC		0.23
ClinPred		0.050	T
GERP RS		-3.7
Varity_R		0.053
gMVP		0.15

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-53455006;