Variant 17-76152363-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052916.3(RNF157):c.1913G>A(p.Cys638Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000539 in 1,604,288 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 3 hom. )

Consequence

RNF157
NM_052916.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Variant links:

Genes affected

RNF157 (HGNC:29402): (ring finger protein 157) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including negative regulation of signal transduction; positive regulation of dendrite extension; and protein autoubiquitination. Predicted to be located in cell body. Predicted to be active in early endosome; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF157 links:

RNF157 (HGNC:):

RNF157 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=0.04508108).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF157	NM_052916.3 linkuse as main transcript	c.1913G>A	p.Cys638Tyr	missense_variant	18/19	ENST00000269391.11	NP_443148.1	Q96PX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF157	ENST00000269391.11 linkuse as main transcript	c.1913G>A	p.Cys638Tyr	missense_variant	18/19	1	NM_052916.3	ENSP00000269391.4		Q96PX1-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000617

AC:

155

AN:

251360

Hom.:

AF XY:

0.000677

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000531

AC:

771

AN:

1452006

Hom.:

Cov.:

AF XY:

0.000559

AC XY:

404

AN XY:

723048

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000767

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000494

Gnomad4 OTH exome

AF:

0.000666

GnomAD4 genome

AF:

0.000617

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000616

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00119

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

Jul 06, 2021

The c.1913G>A (p.C638Y) alteration is located in exon 18 (coding exon 18) of the RNF157 gene. This alteration results from a G to A substitution at nucleotide position 1913, causing the cysteine (C) at amino acid position 638 to be replaced by a tyrosine (Y). 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

0.16

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

N;.;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0050

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.83

MVP

0.84

MPC

0.42

ClinPred

0.053

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.067

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