22-45413909-T-C

Variant names:

• chr22-45413909-T-C
• rs1602108261
• NM_015653.5:c.23T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015653.5(RIBC2):​c.23T>C​(p.Val8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RIBC2 NM_015653.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.109270066).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015653.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIBC2	NM_015653.5	MANE Select	c.23T>C	p.Val8Ala	missense	Exon 1 of 7	NP_056468.3	Q9H4K1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIBC2	ENST00000614167.2	TSL:1 MANE Select	c.23T>C	p.Val8Ala	missense	Exon 1 of 7	ENSP00000483356.1	Q9H4K1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399174 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690036

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.0000280 AC: 1 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078820

Other (OTH) AF: 0.00 AC: 0 AN: 57994

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.017	D
Vest4		0.11
MVP		0.52
ClinPred		0.085	T
GERP RS		3.2
PromoterAI		0.089	Neutral
gMVP		0.27
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1602108261; hg19: chr22-45809790;