X-53430700-A-G

Position:

• chrX-53430700-A-G

Variant summary

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

The NM_001031745.5(RIBC1):​c.968A>G​(p.Glu323Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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=0.2644124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.968A>G	p.Glu323Gly	missense_variant	7/8	ENST00000375327.6	NP_001026915.1
RIBC1	NM_001267053.4	c.623A>G	p.Glu208Gly	missense_variant	6/6		NP_001253982.1
RIBC1	XM_005261988.5	c.968A>G	p.Glu323Gly	missense_variant	7/8		XP_005262045.1
RIBC1	XM_005261990.5	c.623A>G	p.Glu208Gly	missense_variant	6/7		XP_005262047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.968A>G	p.Glu323Gly	missense_variant	7/8	1	NM_001031745.5	ENSP00000364476	P1
RIBC1	ENST00000414955.6	c.623A>G	p.Glu208Gly	missense_variant	6/6	2		ENSP00000401463

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

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

Jan 31, 2024

The c.968A>G (p.E323G) alteration is located in exon 7 (coding exon 5) of the RIBC1 gene. This alteration results from a A to G substitution at nucleotide position 968, causing the glutamic acid (E) at amino acid position 323 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.14
Sift	Benign	0.031	D;T
Sift4G	Benign	0.062	T;T
Polyphen		0.93	.;P
Vest4		0.18
MutPred		0.51		.;Loss of stability (P = 0.1033);
MVP		0.28
MPC		0.82
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.15
gMVP		0.44

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-53457648;