9-113298030-C-G

Variant names:

• chr9-113298030-C-G
• rs746654594
• NM_001371237.1:c.155G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371237.1(RNF183):​c.155G>C​(p.Arg52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNF183 NM_001371237.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 1 publications found

Genes affected

RNF183 (HGNC:28721): (ring finger protein 183) Enables ubiquitin protein ligase activity. Involved in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; protein ubiquitination; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38723105).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371237.1. 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
	RNF183	NM_001371237.1	MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 5 of 5	NP_001358166.1	Q96D59
	RNF183	NM_001371234.1		c.155G>C	p.Arg52Pro	missense	Exon 2 of 2	NP_001358163.1	Q96D59
	RNF183	NM_001371235.1		c.155G>C	p.Arg52Pro	missense	Exon 4 of 4	NP_001358164.1	Q96D59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF183	ENST00000489339.2	TSL:4 MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 5 of 5	ENSP00000508293.1	Q96D59
	RNF183	ENST00000441031.3	TSL:1	c.155G>C	p.Arg52Pro	missense	Exon 2 of 2	ENSP00000417176.1	Q96D59
	RNF183	ENST00000297894.5	TSL:2	c.155G>C	p.Arg52Pro	missense	Exon 4 of 4	ENSP00000417943.1	Q96D59

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	0.55	N
PhyloP100		0.20
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.36
Sift	Benign	0.064	T
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.23
MutPred		0.49		Loss of solvent accessibility (P = 0.0364)
MVP		0.93
MPC		1.1
ClinPred		0.52	D
GERP RS		3.2
Varity_R		0.35
gMVP		0.73
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746654594; hg19: chr9-116060310;