Variant 11-74748914-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001098638.2(RNF169):c.34T>G(p.Ser12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000077 in 1,298,806 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

RNF169
NM_001098638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

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 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity RN169_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16460025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF169	NM_001098638.2 linkuse as main transcript	c.34T>G	p.Ser12Ala	missense_variant	1/6	ENST00000299563.5
RNF169	XM_011544889.4 linkuse as main transcript	c.34T>G	p.Ser12Ala	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF169	ENST00000299563.5 linkuse as main transcript	c.34T>G	p.Ser12Ala	missense_variant	1/6	1	NM_001098638.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.70e-7

AC:

AN:

1298806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

640574

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:

9.76e-7

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

May 03, 2023

The c.34T>G (p.S12A) alteration is located in exon 1 (coding exon 1) of the RNF169 gene. This alteration results from a T to G substitution at nucleotide position 34, causing the serine (S) at amino acid position 12 to be replaced by an alanine (A). 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

0.097

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.96

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.050

REVEL

Benign

0.019

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.36

Vest4

0.25

MutPred

0.30

Loss of glycosylation at S12 (P = 0.0022);

MVP

0.44

MPC

0.17

ClinPred

0.72

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.32

gMVP

0.46

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