17-30971202-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032322.4(RNF135):​c.129C>T​(p.His43His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,524,090 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 12 hom., cov: 33)
Exomes 𝑓: 0.00046 ( 2 hom. )

Consequence

RNF135
NM_032322.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.614

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: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 17-30971202-C-T is Benign according to our data. Variant chr17-30971202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.614 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00524 (798/152298) while in subpopulation AFR AF = 0.0185 (771/41572). AF 95% confidence interval is 0.0175. There are 12 homozygotes in GnomAd4. There are 370 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High AC in GnomAd4 at 798 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF135NM_032322.4 linkc.129C>T p.His43His synonymous_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.129C>T p.His43His synonymous_variant Exon 1 of 5 1 NM_032322.4 ENSP00000328340.5 Q8IUD6-1

Frequencies

GnomAD3 genomes
AF:
0.00522
AC:
795
AN:
152190
Hom.:
12
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0185
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
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:
0.0000147
Gnomad OTH
AF:
0.00191
GnomAD2 exomes
AF:
0.000655
AC:
77
AN:
117566
AF XY:
0.000477
show subpopulations
Gnomad AFR exome
AF:
0.0146
Gnomad AMR exome
AF:
0.00115
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000229
Gnomad OTH exome
AF:
0.000545
GnomAD4 exome
AF:
0.000459
AC:
630
AN:
1371792
Hom.:
2
Cov.:
31
AF XY:
0.000390
AC XY:
264
AN XY:
676668
show subpopulations
African (AFR)
AF:
0.0167
AC:
486
AN:
29178
American (AMR)
AF:
0.00129
AC:
45
AN:
35002
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24656
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34404
South Asian (SAS)
AF:
0.0000256
AC:
2
AN:
78008
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34300
Middle Eastern (MID)
AF:
0.000635
AC:
3
AN:
4726
European-Non Finnish (NFE)
AF:
0.0000195
AC:
21
AN:
1074242
Other (OTH)
AF:
0.00127
AC:
73
AN:
57276
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
41
82
122
163
204
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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
AF:
0.00524
AC:
798
AN:
152298
Hom.:
12
Cov.:
33
AF XY:
0.00497
AC XY:
370
AN XY:
74472
show subpopulations
African (AFR)
AF:
0.0185
AC:
771
AN:
41572
American (AMR)
AF:
0.00144
AC:
22
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67998
Other (OTH)
AF:
0.00189
AC:
4
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
39
78
118
157
196
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00283
Hom.:
1
Bravo
AF:
0.00553

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Mar 23, 2021
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
3.3
DANN
Benign
0.96
PhyloP100
0.61
PromoterAI
0.28
Neutral
Mutation Taster
=100/0
polymorphism

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: rs570839353; hg19: chr17-29298220; API