Variant 17-30971313-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000328381.10(RNF135):c.240C>G(p.Asp80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000841 in 1,534,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

RNF135
ENST00000328381.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.345

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06131646).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF135	NM_032322.4 linkuse as main transcript	c.240C>G	p.Asp80Glu	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.240C>G	p.Asp80Glu	missense_variant	1/5	1	NM_032322.4	ENSP00000328340	P1	Q8IUD6-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

126024

Hom.:

AF XY:

0.0000432

AC XY:

AN XY:

69486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000842

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:

0.0000654

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000861

AC:

119

AN:

1381836

Hom.:

Cov.:

AF XY:

0.0000865

AC XY:

AN XY:

682106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.0000579

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.0000349

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000495

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

Feb 27, 2023

The c.240C>G (p.D80E) 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 240, causing the aspartic acid (D) at amino acid position 80 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0013

T;T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N;N

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.41

N;.;N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0020

B;.;P;.

Vest4

0.016

MutPred

0.39

Gain of MoRF binding (P = 0.1422);Gain of MoRF binding (P = 0.1422);Gain of MoRF binding (P = 0.1422);Gain of MoRF binding (P = 0.1422);

MVP

0.21

MPC

0.084

ClinPred

0.11

GERP RS

1.2

Varity_R

0.039

gMVP

0.074

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