22-45422291-G-T

Position:

• chr22-45422291-G-T

Variant summary

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

The NM_015653.5(RIBC2):​c.558G>T​(p.Glu186Asp) variant causes a missense, splice region 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. 12/15 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.918

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11176664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC2	NM_015653.5	c.558G>T	p.Glu186Asp	missense_variant, splice_region_variant	4/7	ENST00000614167.2	NP_056468.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2	c.558G>T	p.Glu186Asp	missense_variant, splice_region_variant	4/7	1	NM_015653.5	ENSP00000483356.1
RIBC2	ENST00000466226.1	n.240G>T		splice_region_variant, non_coding_transcript_exon_variant	2/4	3
RIBC2	ENST00000621287.1	n.428G>T		splice_region_variant, non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 27, 2024

The c.543G>T (p.E181D) alteration is located in exon 4 (coding exon 4) of the RIBC2 gene. This alteration results from a G to T substitution at nucleotide position 543, causing the glutamic acid (E) at amino acid position 181 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	10
DANN	Benign	0.42
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.80	T
Vest4		0.071
MVP		0.55
ClinPred		0.068	T
GERP RS		3.5
gMVP		0.096

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: chr22-45818171;