9-113297700-A-C

Variant names:

• chr9-113297700-A-C
• NM_001371237.1:c.485T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371237.1(RNF183):​c.485T>G​(p.Ile162Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNF183 NM_001371237.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10605556).

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.485T>G	p.Ile162Ser	missense	Exon 5 of 5	NP_001358166.1	Q96D59
	RNF183	NM_001371234.1		c.485T>G	p.Ile162Ser	missense	Exon 2 of 2	NP_001358163.1	Q96D59
	RNF183	NM_001371235.1		c.485T>G	p.Ile162Ser	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.485T>G	p.Ile162Ser	missense	Exon 5 of 5	ENSP00000508293.1	Q96D59
	RNF183	ENST00000441031.3	TSL:1	c.485T>G	p.Ile162Ser	missense	Exon 2 of 2	ENSP00000417176.1	Q96D59
	RNF183	ENST00000297894.5	TSL:2	c.485T>G	p.Ile162Ser	missense	Exon 4 of 4	ENSP00000417943.1	Q96D59

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

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	0.30
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.090	B
Vest4		0.26
MutPred		0.35		Loss of stability (P = 0.0199)
MVP		0.15
MPC		0.60
ClinPred		0.14	T
GERP RS		4.1
Varity_R		0.12
gMVP		0.86
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr9-116059980;