17-80263746-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001256071.3(RNF213):c.65G>A(p.Gly22Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001256071.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF213 | NM_001256071.3 | c.65G>A | p.Gly22Glu | missense_variant | 2/68 | ENST00000582970.6 | NP_001243000.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF213 | ENST00000582970.6 | c.65G>A | p.Gly22Glu | missense_variant | 2/68 | 1 | NM_001256071.3 | ENSP00000464087.1 | ||
RNF213 | ENST00000319921.4 | c.65G>A | p.Gly22Glu | missense_variant | 2/17 | 1 | ENSP00000324392.4 | |||
RNF213 | ENST00000508628.6 | c.65G>A | p.Gly22Glu | missense_variant | 2/69 | 5 | ENSP00000425956.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727210
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Moyamoya disease 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The missense variant c.65G>A(p.Gly22Glu) in RNF213 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant is absent in gnomAD exomes database. This variant has not been submitted to the ClinVar database. The amino acid change p.Gly22Glu in RNF213 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Multiple lines of computational evidence (SIFT- damaging and MutationTaster- polymorphism) predicts a conflicting evidences on protein structure and function for this variant. The amino acid Gly at position 22 is changed to a Glu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.