chr17-30971211-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032322.4(RNF135):​c.138G>T​(p.Glu46Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

RNF135
NM_032322.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.310

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • overgrowth-macrocephaly-facial dysmorphism syndrome
    Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
  • overgrowth syndrome
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0834097).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF135NM_032322.4 linkc.138G>T p.Glu46Asp 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
RNF135ENST00000328381.10 linkc.138G>T p.Glu46Asp missense_variant Exon 1 of 5 1 NM_032322.4 ENSP00000328340.5 Q8IUD6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.35e-7
AC:
1
AN:
1361426
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
671504
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27866
American (AMR)
AF:
0.00
AC:
0
AN:
33048
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24174
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33224
South Asian (SAS)
AF:
0.00
AC:
0
AN:
76868
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34756
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4562
European-Non Finnish (NFE)
AF:
9.34e-7
AC:
1
AN:
1070222
Other (OTH)
AF:
0.00
AC:
0
AN:
56706
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
2.0
DANN
Benign
0.67
DEOGEN2
Benign
0.0037
T;T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.19
T;T;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.083
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;L;L
PhyloP100
-0.31
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.83
N;.;N;N
REVEL
Benign
0.095
Sift
Benign
0.62
T;.;T;T
Sift4G
Benign
0.33
T;T;T;T
Polyphen
0.14
B;.;P;.
Vest4
0.16
MutPred
0.60
Gain of MoRF binding (P = 0.123);Gain of MoRF binding (P = 0.123);Gain of MoRF binding (P = 0.123);Gain of MoRF binding (P = 0.123);
MVP
0.32
MPC
0.083
ClinPred
0.32
T
GERP RS
-4.7
PromoterAI
-0.16
Neutral
Varity_R
0.072
gMVP
0.22

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

Other links and lift over

dbSNP: rs1364910406; hg19: chr17-29298229; API