Variant chr5-159158734-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000424310.7(RNF145):c.1928C>T(p.Ala643Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,613,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

RNF145
ENST00000424310.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RNF145 links:

RNF145 (HGNC:):

RNF145 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024983883).

BP6

Variant 5-159158734-G-A is Benign according to our data. Variant chr5-159158734-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2278456.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF145	NM_001199383.2 linkuse as main transcript	c.1928C>T	p.Ala643Val	missense_variant	11/11	ENST00000424310.7	NP_001186312.1	Q96MT1-1A8K9Y9Q8NDT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7 linkuse as main transcript	c.1928C>T	p.Ala643Val	missense_variant	11/11	1	NM_001199383.2	ENSP00000409064.2		Q96MT1-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000541

AC:

136

AN:

251166

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000313

AC:

458

AN:

1461642

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

253

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000309

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.027

.;T;T;T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.63

T;.;.;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0025

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

.;N;N;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.63

N;N;N;.;.;N;N

REVEL

Benign

0.19

Sift

Benign

0.25

T;T;T;.;.;T;T

Sift4G

Benign

0.28

T;T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;.;.;.

Vest4

0.023

MVP

0.29

MPC

0.022

ClinPred

0.0098

GERP RS

2.2

Varity_R

0.016

gMVP

0.098

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