Variant 5-159203649-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000424310.7(RNF145):c.-32C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000773 in 1,578,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

RNF145
ENST00000424310.7 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.450

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023764819).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF145	NM_001199383.2 linkuse as main transcript	c.-32C>T		5_prime_UTR_variant	2/11	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.-32C>T		5_prime_UTR_variant	2/11	1	NM_001199383.2	ENSP00000409064.2		Q96MT1-1

Frequencies

GnomAD3 genomes

AF:

0.0000402

AC:

AN:

149414

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:

0.00117

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000540

AC:

AN:

222292

Hom.:

AF XY:

0.0000413

AC XY:

AN XY:

121050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000743

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000812

AC:

116

AN:

1429106

Hom.:

Cov.:

AF XY:

0.0000802

AC XY:

AN XY:

710956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00283

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000401

AC:

AN:

149522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72846

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000578

AC:

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 11, 2022

The c.59C>T (p.S20F) alteration is located in exon 2 (coding exon 2) of the RNF145 gene. This alteration results from a C to T substitution at nucleotide position 59, causing the serine (S) at amino acid position 20 to be replaced by a phenylalanine (F). 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

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.55

T;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-0.67

MutationTaster

Benign

1.0

D;D;D;N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.46

N;.;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;.;D;D

Polyphen

0.0

B;.;.;.

Vest4

0.17

MVP

0.26

MPC

1.1

ClinPred

0.29

GERP RS

2.3

gMVP

0.073

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