NM_022064.5:c.592G>C

Variant names:

• chr3-49698776-G-C
• rs1283626541
• NM_022064.5:c.592G>C

Variant summary

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

The NM_022064.5(RNF123):​c.592G>C​(p.Val198Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF123 NM_022064.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

Genes affected

RNF123 (HGNC:21148): (ring finger protein 123) The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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
RNF123	NM_022064.5	c.592G>C	p.Val198Leu	missense_variant	Exon 9 of 39	ENST00000327697.11	NP_071347.2
RNF123	NR_135218.2	n.678G>C		non_coding_transcript_exon_variant	Exon 9 of 39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF123	ENST00000327697.11	c.592G>C	p.Val198Leu	missense_variant	Exon 9 of 39	1	NM_022064.5	ENSP00000328287.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250868 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135646

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461596 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.95	L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.029	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.56		Loss of catalytic residue at V198 (P = 0.0848);.;
MVP		0.46
MPC		2.3
ClinPred		0.84	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.82

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: rs1283626541; hg19: chr3-49736209;