3-49698124-G-C

Variant names:

• chr3-49698124-G-C
• rs538967921
• NM_022064.5:c.470G>C

Variant summary

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

The NM_022064.5(RNF123):​c.470G>C​(p.Arg157Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,598 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF123 NM_022064.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33

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.470G>C	p.Arg157Pro	missense_variant	Exon 7 of 39	ENST00000327697.11	NP_071347.2
RNF123	NR_135218.2	n.556G>C		non_coding_transcript_exon_variant	Exon 7 of 39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF123	ENST00000327697.11	c.470G>C	p.Arg157Pro	missense_variant	Exon 7 of 39	1	NM_022064.5	ENSP00000328287.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251166 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135748

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: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727104

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.035	N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.042	D;T
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.63		Loss of stability (P = 0.1434);.;
MVP		0.69
MPC		2.6
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs538967921; hg19: chr3-49735557;