rs387907369
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_207111.4(RNF216):c.1791T>A(p.Cys597Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
RNF216
NM_207111.4 stop_gained
NM_207111.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 2.55
Genes affected
RNF216 (HGNC:21698): (ring finger protein 216) This gene encodes a cytoplasmic protein which specifically colocalizes and interacts with the serine/threonine protein kinase, receptor-interacting protein (RIP). Zinc finger domains of the encoded protein are required for its interaction with RIP and for inhibition of TNF- and IL1-induced NF-kappa B activation pathways. The encoded protein may also function as an E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes and transfers it to substrates. Several alternatively spliced transcript variants have been described for this locus but the full-length natures of only some are known. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-5715095-A-T is Pathogenic according to our data. Variant chr7-5715095-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 50913.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNF216 | NM_207111.4 | c.1791T>A | p.Cys597Ter | stop_gained | 11/17 | ENST00000389902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNF216 | ENST00000389902.8 | c.1791T>A | p.Cys597Ter | stop_gained | 11/17 | 1 | NM_207111.4 | P4 | |
RNF216 | ENST00000425013.6 | c.1620T>A | p.Cys540Ter | stop_gained | 11/17 | 1 | A1 | ||
RNF216 | ENST00000389900.8 | c.*908T>A | 3_prime_UTR_variant, NMD_transcript_variant | 10/16 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727114
GnomAD4 exome
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31
AN:
1461600
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31
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14
AN XY:
727114
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cerebellar ataxia-hypogonadism syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 23, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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