Variant 11-74749212-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098638.2(RNF169):c.332C>G(p.Pro111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,098,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RNF169
NM_001098638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023911893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF169	NM_001098638.2 linkuse as main transcript	c.332C>G	p.Pro111Arg	missense_variant	1/6	ENST00000299563.5	NP_001092108.1	Q8NCN4
RNF169	XM_011544889.4 linkuse as main transcript	c.332C>G	p.Pro111Arg	missense_variant	1/6		XP_011543191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF169	ENST00000299563.5 linkuse as main transcript	c.332C>G	p.Pro111Arg	missense_variant	1/6	1	NM_001098638.2	ENSP00000299563.4		Q8NCN4

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

147928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00270

AC:

AN:

370

Hom.:

AF XY:

0.00476

AC XY:

AN XY:

210

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

950740

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

447262

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000270

AC:

AN:

147928

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

72046

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

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

Aug 27, 2024

The c.332C>G (p.P111R) alteration is located in exon 1 (coding exon 1) of the RNF169 gene. This alteration results from a C to G substitution at nucleotide position 332, causing the proline (P) at amino acid position 111 to be replaced by an arginine (R). 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

0.096

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.14

REVEL

Benign

0.023

Sift

Benign

0.10

Sift4G

Benign

0.14

Polyphen

0.38

Vest4

0.26

MVP

0.40

MPC

0.24

ClinPred

0.056

GERP RS

0.44

Varity_R

0.049

gMVP

0.29

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