chr22-45426007-G-C

Position:

• chr22-45426007-G-C

Variant summary

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

The NM_015653.5(RIBC2):​c.735G>C​(p.Leu245Phe) 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. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIBC2 NM_015653.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76

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=0.072554916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC2	NM_015653.5	c.735G>C	p.Leu245Phe	missense_variant	5/7	ENST00000614167.2	NP_056468.3
RIBC2	XM_005261524.5	c.516G>C	p.Leu172Phe	missense_variant	5/7		XP_005261581.1
RIBC2	XM_011530126.3	c.246G>C	p.Leu82Phe	missense_variant	3/5		XP_011528428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2	c.735G>C	p.Leu245Phe	missense_variant	5/7	1	NM_015653.5	ENSP00000483356	P1
RIBC2	ENST00000466226.1	n.417G>C		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.53
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.38	T
Vest4		0.11
MVP		0.36
ClinPred		0.21	T
GERP RS		3.5
gMVP		0.31

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: rs1022477; hg19: chr22-45821887;