3-49700258-T-G

Variant names:

• chr3-49700258-T-G
• NM_022064.5:c.1016T>G

Variant summary

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

The NM_022064.5(RNF123):​c.1016T>G​(p.Met339Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF123 NM_022064.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF123	NM_022064.5	c.1016T>G	p.Met339Arg	missense_variant	Exon 13 of 39	ENST00000327697.11	NP_071347.2
RNF123	NR_135218.2	n.1102T>G		non_coding_transcript_exon_variant	Exon 13 of 39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF123	ENST00000327697.11	c.1016T>G	p.Met339Arg	missense_variant	Exon 13 of 39	1	NM_022064.5	ENSP00000328287.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3 AN: 152096 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

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: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000224 AC: 326 AN: 1455120 Hom.: 0 Cov.: 33 AF XY: 0.000206 AC XY: 149 AN XY: 723938

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.0000673

Gnomad4 ASJ exome AF: 0.000231

Gnomad4 EAS exome AF: 0.000254

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000415

Gnomad4 NFE exome AF: 0.000238

Gnomad4 OTH exome AF: 0.000183

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000197 AC: 3 AN: 152096 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74312

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.021	B;B
Vest4		0.80
MutPred		0.57		Loss of helix (P = 0.0123);.;
MVP		0.90
MPC		0.45
ClinPred		0.88	D
GERP RS		4.4
Varity_R		0.71
gMVP		0.88

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49737691;