22-45417875-A-G

Variant names:

• chr22-45417875-A-G
• NM_015653.5:c.485A>G

Variant summary

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

The NM_015653.5(RIBC2):​c.485A>G​(p.Glu162Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIBC2 NM_015653.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06

Genes affected

RIBC2 (HGNC:13241): (RIB43A domain with coiled-coils 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIBC2	NM_015653.5	c.485A>G	p.Glu162Gly	missense_variant	Exon 3 of 7	ENST00000614167.2	NP_056468.3
RIBC2	XM_005261524.5	c.266A>G	p.Glu89Gly	missense_variant	Exon 3 of 7		XP_005261581.1
RIBC2	XM_017028766.2	c.485A>G	p.Glu162Gly	missense_variant	Exon 3 of 5		XP_016884255.1
RIBC2	XM_011530126.3	c.-303A>G		upstream_gene_variant			XP_011528428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2	c.485A>G	p.Glu162Gly	missense_variant	Exon 3 of 7	1	NM_015653.5	ENSP00000483356.1
RIBC2	ENST00000621287.1	n.355A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3
RIBC2	ENST00000466226.1	n.-132A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.470A>G (p.E157G) alteration is located in exon 3 (coding exon 3) of the RIBC2 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the glutamic acid (E) at amino acid position 157 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	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.78	T
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.0030	D
Vest4		0.73
MVP		0.63
ClinPred		0.99	D
GERP RS		4.6
gMVP		0.33

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: chr22-45813755;