Variant 9-113297844-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10375 hom., cov: 30)

Exomes 𝑓: 0.35 ( 94364 hom. )

Consequence

RNF183
NM_001371237.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0910

Variant links:

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]

RNF183 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RNF183	NM_001371237.1 linkuse as main transcript	c.341A>G	p.Gln114Arg	missense_variant	5/5	ENST00000489339.2	NP_001358166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF183	ENST00000489339.2 linkuse as main transcript	c.341A>G	p.Gln114Arg	missense_variant	5/5	4	NM_001371237.1	ENSP00000508293	P1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55111

AN:

151428

Hom.:

10346

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.358

AC:

88394

AN:

247034

Hom.:

16779

AF XY:

0.367

AC XY:

49205

AN XY:

134034

show subpopulations

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 SAS exome

AF:

0.523

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.:

AF XY:

0.359

AC XY:

260556

AN XY:

724900

show subpopulations

Gnomad4 AFR exome

AF:

0.434

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.516

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.364

AC:

55193

AN:

151546

Hom.:

10375

Cov.:

AF XY:

0.365

AC XY:

26988

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.538

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.351

Hom.:

23729

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

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

LIST_S2

Benign

0.11

.;.;.;T

MetaRNN

Benign

0.00011

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.97

N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.43

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

GERP RS

3.2

Varity_R

0.037

gMVP

0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over