rs773691749
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_032322.4(RNF135):βc.901delβ(p.Gln301ArgfsTer34) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,613,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.00023 ( 0 hom., cov: 32)
Exomes π: 0.00041 ( 0 hom. )
Consequence
RNF135
NM_032322.4 frameshift
NM_032322.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.28
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF135 | NM_032322.4 | c.901del | p.Gln301ArgfsTer34 | frameshift_variant | 5/5 | ENST00000328381.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF135 | ENST00000328381.10 | c.901del | p.Gln301ArgfsTer34 | frameshift_variant | 5/5 | 1 | NM_032322.4 | P1 | |
RNF135 | ENST00000324689.8 | c.*105del | 3_prime_UTR_variant | 4/4 | 1 | ||||
RNF135 | ENST00000443677.6 | c.*105del | 3_prime_UTR_variant | 3/3 | 1 | ||||
RNF135 | ENST00000535306.6 | c.*105del | 3_prime_UTR_variant | 6/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000231 AC: 58AN: 250562Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135432
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GnomAD4 exome AF: 0.000408 AC: 596AN: 1461178Hom.: 0 Cov.: 33 AF XY: 0.000382 AC XY: 278AN XY: 726892
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GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 05, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 30, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at