rs3750534

Variant names:

• chr9-113297844-T-C
• rs3750534
• NM_001371237.1:c.341A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371237.1(RNF183):​c.341A>G​(p.Gln114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,609,848 control chromosomes in the GnomAD database, including 104,739 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10375 hom., cov: 30)
  • Exomes 𝑓: 0.35 (94364 hom.)
• Consequence: RNF183 NM_001371237.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0625368E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF183	NM_001371237.1	c.341A>G	p.Gln114Arg	missense_variant	Exon 5 of 5	ENST00000489339.2	NP_001358166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF183	ENST00000489339.2	c.341A>G	p.Gln114Arg	missense_variant	Exon 5 of 5	4	NM_001371237.1	ENSP00000508293.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55111 AN: 151428 Hom.: 10346 Cov.: 30

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.345

GnomAD2 exomes AF: 0.358 AC: 88394 AN: 247034 AF XY: 0.367

Gnomad AFR exome AF: 0.428

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.416

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.355 AC: 517217 AN: 1458302 Hom.: 94364 Cov.: 38 AF XY: 0.359 AC XY: 260556 AN XY: 724900

African (AFR) AF: 0.434 AC: 14506 AN: 33398

American (AMR) AF: 0.233 AC: 10371 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12360 AN: 25940

East Asian (EAS) AF: 0.437 AC: 17319 AN: 39620

South Asian (SAS) AF: 0.516 AC: 44296 AN: 85902

European-Finnish (FIN) AF: 0.295 AC: 15729 AN: 53292

Middle Eastern (MID) AF: 0.361 AC: 2075 AN: 5750

European-Non Finnish (NFE) AF: 0.341 AC: 378490 AN: 1109672

Other (OTH) AF: 0.366 AC: 22071 AN: 60222

GnomAD4 genome AF: 0.364 AC: 55193 AN: 151546 Hom.: 10375 Cov.: 30 AF XY: 0.365 AC XY: 26988 AN XY: 74022

African (AFR) AF: 0.430 AC: 17757 AN: 41318

American (AMR) AF: 0.268 AC: 4090 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2112 AN: 5076

South Asian (SAS) AF: 0.538 AC: 2572 AN: 4784

European-Finnish (FIN) AF: 0.285 AC: 3002 AN: 10516

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22824 AN: 67824

Other (OTH) AF: 0.350 AC: 737 AN: 2108

Alfa AF: 0.351 Hom.: 42908

Bravo AF: 0.363

TwinsUK AF: 0.332 AC: 1232

ALSPAC AF: 0.339 AC: 1307

ESP6500AA AF: 0.427 AC: 1682

ESP6500EA AF: 0.338 AC: 2814

ExAC AF: 0.364 AC: 43962

Asia WGS AF: 0.497 AC: 1727 AN: 3476

EpiCase AF: 0.341

EpiControl AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.55
DEOGEN2	Benign	0.0028	T;T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.11	.;.;.;T
MetaRNN	Benign	0.00011	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N;N;N;N
PhyloP100		0.091
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.44	N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.94	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.010
MPC		0.38
ClinPred		0.0024	T
GERP RS		3.2
Varity_R		0.037
gMVP		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs3750534; hg19: chr9-116060124; COSMIC: COSV52907421; COSMIC: COSV52907421;