Variant 11-74749236-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098638.2(RNF169):c.356G>A(p.Arg119His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,079,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 0 hom. )

Consequence

RNF169
NM_001098638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

Variant links:

Genes affected

RNF169 (HGNC:26961): (ring finger protein 169) Enables K63-linked polyubiquitin modification-dependent protein binding activity and nucleosome binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of double-strand break repair. Located in cytosol; nuclear lumen; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

RNF169 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020796657).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF169	NM_001098638.2 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	1/6	ENST00000299563.5
RNF169	XM_011544889.4 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF169	ENST00000299563.5 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	1/6	1	NM_001098638.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

148

AN:

148122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000671

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000491

GnomAD3 exomes

AF:

0.000921

AC:

AN:

1086

Hom.:

AF XY:

0.00174

AC XY:

AN XY:

576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00182

AC:

1696

AN:

931650

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

789

AN XY:

437616

show subpopulations

Gnomad4 AFR exome

AF:

0.000331

Gnomad4 AMR exome

AF:

0.000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.00419

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000998

AC:

148

AN:

148228

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

AN XY:

72240

show subpopulations

Gnomad4 AFR

AF:

0.000462

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.000485

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.000752

ExAC

AF:

0.000766

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.356G>A (p.R119H) alteration is located in exon 1 (coding exon 1) of the RNF169 gene. This alteration results from a G to A substitution at nucleotide position 356, causing the arginine (R) at amino acid position 119 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.12

Sift

Uncertain

0.019

Sift4G

Uncertain

0.060

Polyphen

0.97

Vest4

0.26

MVP

0.63

MPC

0.86

ClinPred

0.23

GERP RS

3.4

Varity_R

0.26

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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