chr17-30971202-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032322.4(RNF135):c.129C>T(p.His43=) 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
NM_032322.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.614
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 Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 795 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF135 | NM_032322.4 | c.129C>T | p.His43= | synonymous_variant | 1/5 | ENST00000328381.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF135 | ENST00000328381.10 | c.129C>T | p.His43= | synonymous_variant | 1/5 | 1 | NM_032322.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00522 AC: 795AN: 152190Hom.: 12 Cov.: 33
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GnomAD3 exomes AF: 0.000655 AC: 77AN: 117566Hom.: 0 AF XY: 0.000477 AC XY: 31AN XY: 65014
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GnomAD4 exome AF: 0.000459 AC: 630AN: 1371792Hom.: 2 Cov.: 31 AF XY: 0.000390 AC XY: 264AN XY: 676668
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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
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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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