Variant 17-76155269-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052916.3(RNF157):c.1747G>A(p.Gly583Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RNF157
NM_052916.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10613242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF157	NM_052916.3 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	16/19	ENST00000269391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF157	ENST00000269391.11 linkuse as main transcript	c.1747G>A	p.Gly583Arg	missense_variant	16/19	1	NM_052916.3	P4	Q96PX1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251422

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

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:

0.00000684

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

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

Jun 29, 2023

The c.1747G>A (p.G583R) alteration is located in exon 16 (coding exon 16) of the RNF157 gene. This alteration results from a G to A substitution at nucleotide position 1747, causing the glycine (G) at amino acid position 583 to be replaced by an arginine (R). 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

0.090

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0017

T;.

Eigen

Benign

-0.050

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.64

D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.077

Sift

Benign

0.11

T;.

Sift4G

Benign

0.34

T;.

Polyphen

0.013

B;.

Vest4

0.23

MutPred

0.15

Gain of solvent accessibility (P = 0.0789);Gain of solvent accessibility (P = 0.0789);

MVP

0.61

MPC

0.21

ClinPred

0.22

GERP RS

4.9

Varity_R

0.094

gMVP

0.044

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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