Variant chr5-159161405-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001199383.2(RNF145):c.1487A>G(p.Tyr496Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RNF145
NM_001199383.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF145	NM_001199383.2 link	c.1487A>G	p.Tyr496Cys	missense_variant	10/11	ENST00000424310.7	NP_001186312.1	Q96MT1-1A8K9Y9Q8NDT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7 link	c.1487A>G	p.Tyr496Cys	missense_variant	10/11	1	NM_001199383.2	ENSP00000409064.2		Q96MT1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251480

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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, 2024

The c.1577A>G (p.Y526C) alteration is located in exon 10 (coding exon 10) of the RNF145 gene. This alteration results from a A to G substitution at nucleotide position 1577, causing the tyrosine (Y) at amino acid position 526 to be replaced by a cysteine (C). 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

0.28

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

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

Eigen

Benign

-0.020

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;.;.;D;D;D;D

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.70

D;D;D;D;D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.34

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

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.4

D;D;D;.;.;D;D

REVEL

Uncertain

0.55

Sift

Benign

0.066

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

Sift4G

Benign

0.13

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

Polyphen

0.057

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

Vest4

0.90

MutPred

0.53

.;Loss of MoRF binding (P = 0.0903);Loss of MoRF binding (P = 0.0903);Loss of MoRF binding (P = 0.0903);.;.;.;

MVP

0.88

MPC

2.0

ClinPred

0.43

GERP RS

6.1

Varity_R

0.36

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

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