Variant 8-100264775-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_183419.4(RNF19A):c.1202G>A(p.Arg401His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,611,804 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 17 hom. )

Consequence

RNF19A
NM_183419.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

RNF19A (HGNC:13432): (ring finger protein 19A, RBR E3 ubiquitin protein ligase) This gene encodes a member of the ring between ring fingers (RBR) protein family, and the encoded protein contains two RING-finger motifs and an in between RING fingers motif. This protein is an E3 ubiquitin ligase that is localized to Lewy bodies, and ubiquitylates synphilin-1, which is an interacting protein of alpha synuclein in neurons. The encoded protein may be involved in amyotrophic lateral sclerosis and Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RNF19A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, RNF19A

BP4

Computational evidence support a benign effect (MetaRNN=0.06466049).

BP6

Variant 8-100264775-C-T is Benign according to our data. Variant chr8-100264775-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658713.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF19A	NM_183419.4 linkuse as main transcript	c.1202G>A	p.Arg401His	missense_variant	6/10	ENST00000341084.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF19A	ENST00000341084.7 linkuse as main transcript	c.1202G>A	p.Arg401His	missense_variant	6/10	5	NM_183419.4	P1	Q9NV58-1
RNF19A	ENST00000519449.5 linkuse as main transcript	c.1202G>A	p.Arg401His	missense_variant	7/11	1		P1	Q9NV58-1
RNF19A	ENST00000523255.5 linkuse as main transcript	n.147G>A		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00136

AC:

342

AN:

250836

Hom.:

AF XY:

0.00164

AC XY:

223

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00730

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000811

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000884

AC:

1290

AN:

1459716

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

774

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.000479

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000958

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00693

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000533

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000744

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00170

AC:

206

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

RNF19A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

0.0077

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.065

T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

D;D

REVEL

Pathogenic

0.81

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.049

D;D

Polyphen

1.0

D;D

Vest4

0.94

MVP

0.81

MPC

2.2

ClinPred

0.37

GERP RS

5.2

Varity_R

0.33

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over