17-80287905-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001256071.3(RNF213):c.352T>C(p.Cys118Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,577,388 control chromosomes in the GnomAD database, including 11 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 Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 10 hom. )

Consequence

RNF213
NM_001256071.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -1.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036865473).

BP6

Variant 17-80287905-T-C is Benign according to our data. Variant chr17-80287905-T-C is described in ClinVar as [Benign]. Clinvar id is 417835.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00171 (261/152322) while in subpopulation NFE AF= 0.000779 (53/68016). AF 95% confidence interval is 0.000612. There are 1 homozygotes in gnomad4. There are 190 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF213	NM_001256071.3 link	c.352T>C	p.Cys118Arg	missense_variant	Exon 4 of 68	ENST00000582970.6	NP_001243000.2	Q63HN8A0A0A0MTR7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF213	ENST00000582970.6 link	c.352T>C	p.Cys118Arg	missense_variant	Exon 4 of 68	1	NM_001256071.3	ENSP00000464087.1	A0A0A0MTR7
RNF213	ENST00000319921.4 link	c.352T>C	p.Cys118Arg	missense_variant	Exon 4 of 17	1		ENSP00000324392.4	Q63HN8-5
RNF213	ENST00000508628.6 link	c.499T>C	p.Cys167Arg	missense_variant	Exon 5 of 69	5		ENSP00000425956.2	A0A0A0MTC1
RNF213	ENST00000559070.5 link	n.-54T>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

261

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00234

AC:

442

AN:

188770

Hom.:

AF XY:

0.00216

AC XY:

219

AN XY:

101210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000512

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.00136

AC:

1936

AN:

1425066

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

934

AN XY:

706148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000624

Gnomad4 AMR exome

AF:

0.000442

Gnomad4 ASJ exome

AF:

0.0000783

Gnomad4 EAS exome

AF:

0.000542

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.000898

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152322

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000933

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00157

AC:

188

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Moyamoya disease 2

Uncertain:1

Mar 03, 2017

UMR-S1161, Institut national de la santé et de la recherche médicale

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

not provided

Benign:1

Dec 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.023

DANN

Benign

0.44

DEOGEN2

Benign

0.018

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.31

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.92

N;.;N

REVEL

Benign

0.035

Sift

Benign

0.63

T;.;T

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.10

MVP

0.45

MPC

0.59

ClinPred

0.033

GERP RS

-3.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

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