Variant chr22-31187165-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152267.4(RNF185):c.71G>A(p.Ser24Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000027 ( 0 hom. )

Consequence

RNF185
NM_152267.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

RNF185 (HGNC:26783): (ring finger protein 185) Enables ubiquitin binding activity; ubiquitin protein ligase activity; and ubiquitin-like protein conjugating enzyme binding activity. Involved in positive regulation of ERAD pathway; protein autoubiquitination; and ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RNF185 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=0.19656113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF185	NM_152267.4 linkuse as main transcript	c.71G>A	p.Ser24Asn	missense_variant	2/7	ENST00000326132.11	NP_689480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF185	ENST00000326132.11 linkuse as main transcript	c.71G>A	p.Ser24Asn	missense_variant	2/7	1	NM_152267.4	ENSP00000320508	P1	Q96GF1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250630

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135548

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461444

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727046

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:

0.0000324

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 06, 2022

The c.71G>A (p.S24N) alteration is located in exon 2 (coding exon 1) of the RNF185 gene. This alteration results from a G to A substitution at nucleotide position 71, causing the serine (S) at amino acid position 24 to be replaced by an asparagine (N). 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

0.090

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.070

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

.;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Uncertain

0.0092

MutationAssessor

Benign

0.69

N;.;N

MutationTaster

Benign

0.88

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.25

N;.;N

REVEL

Uncertain

0.51

Sift

Benign

0.46

T;.;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.12

B;.;B

Vest4

0.27

MutPred

0.19

Loss of phosphorylation at S24 (P = 0.0096);Loss of phosphorylation at S24 (P = 0.0096);Loss of phosphorylation at S24 (P = 0.0096);

MVP

0.78

MPC

0.29

ClinPred

0.22

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.32

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