Variant 17-30971302-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000328381.10(RNF135):c.229C>G(p.Leu77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

RNF135
ENST00000328381.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.796

Variant links:

Genes affected

RNF135 (HGNC:21158): (ring finger protein 135) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

RNF135 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF135	NM_032322.4 linkuse as main transcript	c.229C>G	p.Leu77Val	missense_variant	1/5	ENST00000328381.10	NP_115698.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF135	ENST00000328381.10 linkuse as main transcript	c.229C>G	p.Leu77Val	missense_variant	1/5	1	NM_032322.4	ENSP00000328340	P1	Q8IUD6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

124432

Hom.:

AF XY:

0.00

AC XY:

AN XY:

68706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000423

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380410

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Mar 15, 2024

The c.229C>G (p.L77V) alteration is located in exon 1 (coding exon 1) of the RNF135 gene. This alteration results from a C to G substitution at nucleotide position 229, causing the leucine (L) at amino acid position 77 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.00098

T;T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.51

N;.;N;N

REVEL

Benign

0.081

Sift

Benign

0.57

T;.;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.24

B;.;D;.

Vest4

0.023

MutPred

0.47

Loss of ubiquitination at K74 (P = 0.0816);Loss of ubiquitination at K74 (P = 0.0816);Loss of ubiquitination at K74 (P = 0.0816);Loss of ubiquitination at K74 (P = 0.0816);

MVP

0.15

MPC

0.11

ClinPred

0.15

GERP RS

-1.1

Varity_R

0.048

gMVP

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.38

Position offset: -1

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