chr17-80373064-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS1_Supporting
The NM_001256071.3(RNF213):c.12841C>T(p.Arg4281Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,874 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 other (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
RNF213
NM_001256071.3 missense
NM_001256071.3 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: -0.0940
Genes affected
RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.831
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000171 (25/1461786) while in subpopulation SAS AF= 0.000151 (13/86256). AF 95% confidence interval is 0.0000888. There are 0 homozygotes in gnomad4_exome. There are 19 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF213 | NM_001256071.3 | c.12841C>T | p.Arg4281Trp | missense_variant | Exon 49 of 68 | ENST00000582970.6 | NP_001243000.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF213 | ENST00000582970.6 | c.12841C>T | p.Arg4281Trp | missense_variant | Exon 49 of 68 | 1 | NM_001256071.3 | ENSP00000464087.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152088Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250844Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135776
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461786Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727204
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
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ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Anaplastic ependymoma Other:1
other, no assertion criteria provided | clinical testing | Donald Williams Parsons Laboratory, Baylor College of Medicine | May 01, 2016 | - 3: Mutations in other consensus cancer genes, not currently considered targetable |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;D
Vest4
MVP
MPC
0.66
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at