Variant 11-74749032-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000299563.5(RNF169):c.152C>T(p.Ser51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF169
ENST00000299563.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08550307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF169	NM_001098638.2 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	1/6	ENST00000299563.5	NP_001092108.1
RNF169	XM_011544889.4 linkuse as main transcript	c.152C>T	p.Ser51Leu	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.152C>T	p.Ser51Leu	missense_variant	1/6	1	NM_001098638.2	ENSP00000299563	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1323528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

652040

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 19, 2023

The c.152C>T (p.S51L) alteration is located in exon 1 (coding exon 1) of the RNF169 gene. This alteration results from a C to T substitution at nucleotide position 152, causing the serine (S) at amino acid position 51 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.96

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.050

REVEL

Benign

0.019

Sift

Benign

0.19

Sift4G

Benign

0.28

Polyphen

0.082

Vest4

0.14

MutPred

0.19

Loss of phosphorylation at S51 (P = 0.017);

MVP

0.37

MPC

0.18

ClinPred

0.12

GERP RS

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.044

gMVP

0.35

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over