Variant 17-76158415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_052916.3(RNF157):c.1391C>T(p.Pro464Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,612,554 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 116 hom. )

Consequence

RNF157
NM_052916.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.277

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004362017).

BP6

Variant 17-76158415-G-A is Benign according to our data. Variant chr17-76158415-G-A is described in ClinVar as [Benign]. Clinvar id is 791506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF157	NM_052916.3 linkuse as main transcript	c.1391C>T	p.Pro464Leu	missense_variant	13/19	ENST00000269391.11	NP_443148.1	Q96PX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF157	ENST00000269391.11 linkuse as main transcript	c.1391C>T	p.Pro464Leu	missense_variant	13/19	1	NM_052916.3	ENSP00000269391.4	Q96PX1-1
RNF157	ENST00000647930.1 linkuse as main transcript	c.1391C>T	p.Pro464Leu	missense_variant	13/19			ENSP00000497353.1	A0A3B3ISM3
RNF157	ENST00000319945.10 linkuse as main transcript	c.1391C>T	p.Pro464Leu	missense_variant	13/18	2		ENSP00000321837.4	Q96PX1-2
RNF157	ENST00000592869.1 linkuse as main transcript	n.109C>T		non_coding_transcript_exon_variant	1/5	4

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1152

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00821

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00729

AC:

1832

AN:

251160

Hom.:

AF XY:

0.00700

AC XY:

950

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00772

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.0110

AC:

16124

AN:

1460348

Hom.:

116

Cov.:

AF XY:

0.0106

AC XY:

7682

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.00774

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00976

GnomAD4 genome

AF:

0.00757

AC:

1152

AN:

152206

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

513

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00821

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00723

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.00739

AC:

897

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.00960

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.9

DANN

Benign

0.64

DEOGEN2

Benign

0.0058

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.34

N;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

N;.;N

REVEL

Benign

0.022

Sift

Benign

0.38

T;.;T

Sift4G

Benign

0.44

T;.;T

Polyphen

0.0

B;.;B

Vest4

0.11

MVP

0.32

MPC

0.14

ClinPred

0.0013

GERP RS

-0.30

Varity_R

0.025

gMVP

0.19

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