9-113298131-G-T

Variant names:

• chr9-113298131-G-T
• rs779511407
• NM_001371237.1:c.54C>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.54C>A​(p.Asn18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF183 NM_001371237.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• 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=0.31907427).

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.54C>A	p.Asn18Lys	missense	Exon 5 of 5	NP_001358166.1	Q96D59
	RNF183	NM_001371234.1		c.54C>A	p.Asn18Lys	missense	Exon 2 of 2	NP_001358163.1	Q96D59
	RNF183	NM_001371235.1		c.54C>A	p.Asn18Lys	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.54C>A	p.Asn18Lys	missense	Exon 5 of 5	ENSP00000508293.1	Q96D59
	RNF183	ENST00000441031.3	TSL:1	c.54C>A	p.Asn18Lys	missense	Exon 2 of 2	ENSP00000417176.1	Q96D59
	RNF183	ENST00000297894.5	TSL:2	c.54C>A	p.Asn18Lys	missense	Exon 4 of 4	ENSP00000417943.1	Q96D59

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.2	L
PhyloP100		2.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.47		Gain of methylation at N18 (P = 0.0018)
MVP		0.91
MPC		1.1
ClinPred		0.77	D
GERP RS		4.2
Varity_R		0.17
gMVP		0.70
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: rs779511407; hg19: chr9-116060411;