Variant 3-196472333-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152617.4(RNF168):c.1202C>A(p.Pro401Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,568 control chromosomes in the GnomAD database, including 287,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20697 hom., cov: 32)

Exomes 𝑓: 0.59 ( 266449 hom. )

Consequence

RNF168
NM_152617.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

RNF168 (HGNC:26661): (ring finger protein 168) This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]

RNF168 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.641032E-5).

BP6

Variant 3-196472333-G-T is Benign according to our data. Variant chr3-196472333-G-T is described in ClinVar as [Benign]. Clinvar id is 403381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-196472333-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF168	NM_152617.4 linkuse as main transcript	c.1202C>A	p.Pro401Gln	missense_variant	6/6	ENST00000318037.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF168	ENST00000318037.3 linkuse as main transcript	c.1202C>A	p.Pro401Gln	missense_variant	6/6	1	NM_152617.4	P1
RNF168	ENST00000437070.1 linkuse as main transcript	c.*774C>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75789

AN:

151904

Hom.:

20700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.511

GnomAD3 exomes

AF:

0.536

AC:

134718

AN:

251322

Hom.:

39033

AF XY:

0.554

AC XY:

75260

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.661

Gnomad NFE exome

AF:

0.618

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.595

AC:

869575

AN:

1461548

Hom.:

266449

Cov.:

AF XY:

0.598

AC XY:

434639

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.614

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.621

Gnomad4 FIN exome

AF:

0.663

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.580

GnomAD4 genome

AF:

0.499

AC:

75788

AN:

152020

Hom.:

20697

Cov.:

AF XY:

0.499

AC XY:

37046

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.614

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.582

Hom.:

57988

Bravo

AF:

0.468

TwinsUK

AF:

0.619

AC:

2297

ALSPAC

AF:

0.624

AC:

2405

ESP6500AA

AF:

0.312

AC:

1373

ESP6500EA

AF:

0.623

AC:

5354

ExAC

AF:

0.540

AC:

65614

Asia WGS

AF:

0.397

AC:

1380

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

RIDDLE syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.013

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.67

MetaRNN

Benign

0.000036

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

REVEL

Benign

0.059

Sift

Benign

0.058

Sift4G

Benign

0.25

Polyphen

0.80

Vest4

0.29

MPC

0.21

ClinPred

0.016

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.069

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over