Variant 17-30971395-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000328381.10(RNF135):c.322T>C(p.Ser108Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 1,522,404 control chromosomes in the GnomAD database, including 17,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 9582 hom., cov: 33)

Exomes 𝑓: 0.025 ( 7575 hom. )

Consequence

RNF135
ENST00000328381.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.76

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.844231E-6).

BP6

Variant 17-30971395-T-C is Benign according to our data. Variant chr17-30971395-T-C is described in ClinVar as [Benign]. Clinvar id is 1296606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF135	NM_032322.4 linkuse as main transcript	c.322T>C	p.Ser108Pro	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.322T>C	p.Ser108Pro	missense_variant	1/5	1	NM_032322.4	ENSP00000328340	P1	Q8IUD6-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30338

AN:

152032

Hom.:

9551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0777

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.0339

AC:

3896

AN:

114962

Hom.:

679

AF XY:

0.0303

AC XY:

1941

AN XY:

63954

show subpopulations

Gnomad AFR exome

AF:

0.694

Gnomad AMR exome

AF:

0.0391

Gnomad ASJ exome

AF:

0.00705

Gnomad EAS exome

AF:

0.000365

Gnomad SAS exome

AF:

0.0288

Gnomad FIN exome

AF:

0.00637

Gnomad NFE exome

AF:

0.00936

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0250

AC:

34240

AN:

1370264

Hom.:

7575

Cov.:

AF XY:

0.0233

AC XY:

15787

AN XY:

676426

show subpopulations

Gnomad4 AFR exome

AF:

0.701

Gnomad4 AMR exome

AF:

0.0461

Gnomad4 ASJ exome

AF:

0.00723

Gnomad4 EAS exome

AF:

0.0000893

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.00600

Gnomad4 NFE exome

AF:

0.00637

Gnomad4 OTH exome

AF:

0.0528

GnomAD4 genome

AF:

0.200

AC:

30414

AN:

152140

Hom.:

9582

Cov.:

AF XY:

0.193

AC XY:

14382

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.673

Gnomad4 AMR

AF:

0.0775

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.0816

Hom.:

1208

Bravo

AF:

0.224

ESP6500AA

AF:

0.378

AC:

1011

ESP6500EA

AF:

0.00561

AC:

ExAC

AF:

0.0305

AC:

1412

Asia WGS

AF:

0.0530

AC:

186

AN:

3470

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	GeneDx	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.88

DANN

Benign

0.31

DEOGEN2

Benign

0.011

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00037

LIST_S2

Benign

0.27

T;T;T;T

MetaRNN

Benign

0.0000058

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.3

N;.;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.70

PROVEAN

Benign

1.1

N;.;N;N

REVEL

Benign

0.038

Sift

Benign

0.34

T;.;T;T

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.088

MPC

0.11

ClinPred

0.0069

GERP RS

1.7

Varity_R

0.057

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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