X-53430582-G-A

Position:

• chrX-53430582-G-A

Variant summary

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

The NM_001031745.5(RIBC1):​c.850G>A​(p.Ala284Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,621 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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: 9.2e-7 (0 hom. 1 hem.)
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69

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=0.14645606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.850G>A	p.Ala284Thr	missense_variant	7/8	ENST00000375327.6	NP_001026915.1
RIBC1	NM_001267053.4	c.505G>A	p.Ala169Thr	missense_variant	6/6		NP_001253982.1
RIBC1	XM_005261988.5	c.850G>A	p.Ala284Thr	missense_variant	7/8		XP_005262045.1
RIBC1	XM_005261990.5	c.505G>A	p.Ala169Thr	missense_variant	6/7		XP_005262047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.850G>A	p.Ala284Thr	missense_variant	7/8	1	NM_001031745.5	ENSP00000364476	P1
RIBC1	ENST00000414955.6	c.505G>A	p.Ala169Thr	missense_variant	6/6	2		ENSP00000401463

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092621 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 1 AN XY: 358711

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

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

Jul 12, 2022

The c.850G>A (p.A284T) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a G to A substitution at nucleotide position 850, causing the alanine (A) at amino acid position 284 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	.;T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.086
Sift	Benign	0.63	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.066	.;B
Vest4		0.051
MutPred		0.53		.;Gain of phosphorylation at A284 (P = 0.0457);
MVP		0.41
MPC		0.39
ClinPred		0.45	T
GERP RS		2.8
Varity_R		0.13
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-53457530;