X-53429937-A-G

Position:

• chrX-53429937-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000375327.6(RIBC1):​c.628A>G​(p.Met210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,733 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: RIBC1 ENST00000375327.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08489689).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.628A>G	p.Met210Val	missense_variant	6/8	ENST00000375327.6	NP_001026915.1
RIBC1	NM_001267053.4	c.283A>G	p.Met95Val	missense_variant	5/6		NP_001253982.1
RIBC1	XM_005261988.5	c.628A>G	p.Met210Val	missense_variant	6/8		XP_005262045.1
RIBC1	XM_005261990.5	c.283A>G	p.Met95Val	missense_variant	5/7		XP_005262047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.628A>G	p.Met210Val	missense_variant	6/8	1	NM_001031745.5	ENSP00000364476.3
RIBC1	ENST00000414955.6	c.283A>G	p.Met95Val	missense_variant	5/6	2		ENSP00000401463.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095733 Hom.: 0 Cov.: 30 AF XY: 0.00000554 AC XY: 2 AN XY: 361301

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 24

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000189

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

Jun 19, 2024

The c.628A>G (p.M210V) alteration is located in exon 6 (coding exon 4) of the RIBC1 gene. This alteration results from a A to G substitution at nucleotide position 628, causing the methionine (M) at amino acid position 210 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	0.071
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.37
DEOGEN2	Benign	0.020	.;T
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.51	.;N
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.028
Sift	Benign	0.35	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0060	.;B
Vest4		0.13
MutPred		0.45		.;Loss of MoRF binding (P = 0.1186);
MVP		0.20
MPC		0.22
ClinPred		0.14	T
GERP RS		1.7
Varity_R		0.084
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs1349911250; hg19: chrX-53456885;