rs1463164474

Variant names:

• chr3-49700506-T-A
• rs1463164474
• NM_022064.5:c.1145T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-49700506-T-A
• chr3-49700506-T-C

Variant summary

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

The NM_022064.5(RNF123):​c.1145T>A​(p.Met382Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,210 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RNF123 NM_022064.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66

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.1145T>A	p.Met382Lys	missense_variant	Exon 14 of 39	ENST00000327697.11	NP_071347.2
RNF123	NR_135218.2	n.1231T>A		non_coding_transcript_exon_variant	Exon 14 of 39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF123	ENST00000327697.11	c.1145T>A	p.Met382Lys	missense_variant	Exon 14 of 39	1	NM_022064.5	ENSP00000328287.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.31	B;P
Vest4		0.84
MutPred		0.48		Gain of catalytic residue at M382 (P = 0.0405);.;
MVP		0.86
MPC		0.43
ClinPred		0.68	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
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: rs1463164474; hg19: chr3-49737939;