17-30971372-A-G

Variant names:

Variant summary

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

The NM_032322.4(RNF135):c.299A>G(p.His100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,527,714 control chromosomes in the GnomAD database, including 30 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 28 hom. )

Consequence

RNF135
NM_032322.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.202

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003282249).

BP6

Variant 17-30971372-A-G is Benign according to our data. Variant chr17-30971372-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 436547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-30971372-A-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 573 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF135	NM_032322.4 link	c.299A>G	p.His100Arg	missense_variant	Exon 1 of 5	ENST00000328381.10	NP_115698.3	Q8IUD6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF135	ENST00000328381.10 link	c.299A>G	p.His100Arg	missense_variant	Exon 1 of 5	1	NM_032322.4	ENSP00000328340.5		Q8IUD6-1

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

574

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00546

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00337

AC:

394

AN:

117010

Hom.:

AF XY:

0.00322

AC XY:

209

AN XY:

64906

show subpopulations

Gnomad AFR exome

AF:

0.000712

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.000663

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00213

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00530

Gnomad OTH exome

AF:

0.00308

GnomAD4 exome

AF:

0.00533

AC:

7335

AN:

1375538

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

3551

AN XY:

678924

show subpopulations

Gnomad4 AFR exome

AF:

0.000937

Gnomad4 AMR exome

AF:

0.000487

Gnomad4 ASJ exome

AF:

0.000445

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.00602

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00377

AC:

573

AN:

152176

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

269

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.00546

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00532

Hom.:

Bravo

AF:

0.00309

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00202

AC:

ExAC

AF:

0.000998

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RNF135: BS1, BS2 -

not specified

Benign:1

Jan 09, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.16

DANN

Benign

0.16

DEOGEN2

Benign

0.0023

T;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.28

T;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.61

N;.;N;N

REVEL

Benign

0.012

Sift

Benign

0.20

T;.;T;T

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.054

MVP

0.30

MPC

0.11

ClinPred

0.015

GERP RS

-1.2

Varity_R

0.033

gMVP

0.049

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