chr3-49699675-G-A

Variant names:

• chr3-49699675-G-A
• rs770997519
• NM_022064.5:c.887G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022064.5(RNF123):​c.887G>A​(p.Arg296Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.000036 (0 hom.)
• Consequence: RNF123 NM_022064.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07995266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022064.5. 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
	RNF123	NM_022064.5	MANE Select	c.887G>A	p.Arg296Gln	missense	Exon 12 of 39	NP_071347.2
	RNF123	NR_135218.2		n.973G>A		non_coding_transcript_exon	Exon 12 of 39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF123	ENST00000327697.11	TSL:1 MANE Select	c.887G>A	p.Arg296Gln	missense	Exon 12 of 39	ENSP00000328287.6	Q5XPI4-1
	RNF123	ENST00000432042.5	TSL:1	c.449G>A	p.Arg150Gln	missense	Exon 9 of 24	ENSP00000392443.1	C9J266
	RNF123	ENST00000457726.5	TSL:1	n.887G>A		non_coding_transcript_exon	Exon 12 of 39	ENSP00000394369.1	C9JS59

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250940 AF XY: 0.0000442

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461558 Hom.: 0 Cov.: 33 AF XY: 0.0000344 AC XY: 25 AN XY: 727106

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111956

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

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	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.076
Sift	Benign	0.48	T
Sift4G	Benign	0.19	T
Polyphen		0.15	B
Vest4		0.26
MutPred		0.42		Gain of sheet (P = 0.0011)
MVP		0.30
MPC		0.30
ClinPred		0.021	T
GERP RS		2.3
Varity_R		0.016
gMVP		0.32
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770997519; hg19: chr3-49737108; COSMIC: COSV59691901; COSMIC: COSV59691901;