Variant rs5749088 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001017981.2(RNF215):c.964G>A(p.Ala322Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,820 control chromosomes in the GnomAD database, including 40,898 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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 0.18 ( 2979 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37919 hom. )

Consequence

RNF215
NM_001017981.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Variant links:

Genes affected

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RNF215 links:

RNF215 (HGNC:):

RNF215 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF215	NM_001017981.2 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	7/9	ENST00000382363.8	NP_001017981.1	Q9Y6U7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF215	ENST00000382363.8 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	7/9	1	NM_001017981.2	ENSP00000371800.3	Q9Y6U7
RNF215	ENST00000215798.10 linkuse as main transcript	c.775G>A	p.Ala259Thr	missense_variant	7/8	5		ENSP00000215798.6	H0Y2L4
RNF215	ENST00000463319.1 linkuse as main transcript	n.716G>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27653

AN:

152036

Hom.:

2980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.0957

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.191

AC:

48009

AN:

251062

Hom.:

5251

AF XY:

0.195

AC XY:

26444

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.221

AC:

323406

AN:

1461666

Hom.:

37919

Cov.:

AF XY:

0.219

AC XY:

159338

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0794

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.182

AC:

27648

AN:

152154

Hom.:

2979

Cov.:

AF XY:

0.176

AC XY:

13085

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0835

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.0954

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.241

Hom.:

9752

Bravo

AF:

0.184

TwinsUK

AF:

0.234

AC:

867

ALSPAC

AF:

0.252

AC:

973

ESP6500AA

AF:

0.0840

AC:

370

ESP6500EA

AF:

0.256

AC:

2198

ExAC

AF:

0.189

AC:

22999

Asia WGS

AF:

0.128

AC:

447

AN:

3478

EpiCase

AF:

0.265

EpiControl

AF:

0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0081

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.036

Sift

Benign

0.35

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.018

MPC

0.34

ClinPred

0.0023

GERP RS

-6.3

Varity_R

0.027

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.81

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.81

Position offset: 3

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