17-80353655-G-A

Position:

chr17-80353655-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_001256071.3(RNF213):c.10567G>A(p.Gly3523Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,614,196 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 5 hom. )

Consequence

RNF213
NM_001256071.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.639

Variant links:

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RNF213 links:

RNF213-AS1 (HGNC:):

RNF213-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RNF213. . Gene score misZ 2.3013 (greater than the threshold 3.09). Trascript score misZ 4.9274 (greater than threshold 3.09). GenCC has associacion of gene with Moyamoya disease 2.

BP4

Computational evidence support a benign effect (MetaRNN=0.007961661).

BP6

Variant 17-80353655-G-A is Benign according to our data. Variant chr17-80353655-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 733381.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High Homozygotes in GnomAdExome4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF213	NM_001256071.3 linkuse as main transcript	c.10567G>A	p.Gly3523Arg	missense_variant	34/68	ENST00000582970.6	NP_001243000.2	Q63HN8A0A0A0MTR7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF213	ENST00000582970.6 linkuse as main transcript	c.10567G>A	p.Gly3523Arg	missense_variant	34/68	1	NM_001256071.3	ENSP00000464087.1	A0A0A0MTR7
RNF213	ENST00000508628.6 linkuse as main transcript	c.10714G>A	p.Gly3572Arg	missense_variant	35/69	5		ENSP00000425956.2	A0A0A0MTC1
RNF213-AS1	ENST00000575034.5 linkuse as main transcript	n.1824C>T		non_coding_transcript_exon_variant	2/2	2
RNF213-AS1	ENST00000613190.1 linkuse as main transcript	n.157C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000270

AC:

AN:

251402

Hom.:

AF XY:

0.000419

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000135

AC:

198

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

153

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2023	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31785789) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.6

DANN

Benign

0.57

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.050

Sift

Benign

0.47

T;.

Sift4G

Benign

0.29

T;T

Vest4

0.10

MVP

0.29

MPC

0.39

ClinPred

0.049

GERP RS

-2.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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