rs753078031

Variant names:

• chr9-113297616-C-T
• rs753078031
• NM_001371237.1:c.569G>A

Variant summary

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

The NM_001371237.1(RNF183):​c.569G>A​(p.Gly190Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,596,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: RNF183 NM_001371237.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• 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=0.36909112).

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.569G>A	p.Gly190Asp	missense	Exon 5 of 5	NP_001358166.1	Q96D59
	RNF183	NM_001371234.1		c.569G>A	p.Gly190Asp	missense	Exon 2 of 2	NP_001358163.1	Q96D59
	RNF183	NM_001371235.1		c.569G>A	p.Gly190Asp	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.569G>A	p.Gly190Asp	missense	Exon 5 of 5	ENSP00000508293.1	Q96D59
	RNF183	ENST00000441031.3	TSL:1	c.569G>A	p.Gly190Asp	missense	Exon 2 of 2	ENSP00000417176.1	Q96D59
	RNF183	ENST00000297894.5	TSL:2	c.569G>A	p.Gly190Asp	missense	Exon 4 of 4	ENSP00000417943.1	Q96D59

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152110 Hom.: 0 Cov.: 31

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236726 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000713 AC: 103 AN: 1444848 Hom.: 0 Cov.: 30 AF XY: 0.0000670 AC XY: 48 AN XY: 716734

African (AFR) AF: 0.00 AC: 0 AN: 33222

American (AMR) AF: 0.00 AC: 0 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 83332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000898 AC: 99 AN: 1102254

Other (OTH) AF: 0.0000670 AC: 4 AN: 59716

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152110 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000734 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000165 AC: 2

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	0.18
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0087	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.46		Loss of catalytic residue at V191 (P = 0.0595)
MVP		0.64
MPC		1.3
ClinPred		0.75	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.95
Mutation Taster		=84/16	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

dbSNP: rs753078031; hg19: chr9-116059896;