chr1-44644728-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018150.4(RNF220):āc.1157A>Gā(p.Glu386Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,614,172 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00026 ( 0 hom., cov: 32)
Exomes š: 0.00033 ( 1 hom. )
Consequence
RNF220
NM_018150.4 missense
NM_018150.4 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 8.49
Genes affected
RNF220 (HGNC:25552): (ring finger protein 220) Predicted to enable ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3781018).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF220 | NM_018150.4 | c.1157A>G | p.Glu386Gly | missense_variant | 9/15 | ENST00000361799.7 | NP_060620.2 | |
LOC107984950 | XR_001738031.2 | n.4307+632T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF220 | ENST00000361799.7 | c.1157A>G | p.Glu386Gly | missense_variant | 9/15 | 1 | NM_018150.4 | ENSP00000354872 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000199 AC: 50AN: 251434Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135892
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GnomAD4 exome AF: 0.000332 AC: 486AN: 1461834Hom.: 1 Cov.: 30 AF XY: 0.000327 AC XY: 238AN XY: 727218
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GnomAD4 genome AF: 0.000263 AC: 40AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.1157A>G (p.E386G) alteration is located in exon 9 (coding exon 8) of the RNF220 gene. This alteration results from a A to G substitution at nucleotide position 1157, causing the glutamic acid (E) at amino acid position 386 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;D
Sift4G
Benign
T;T;T;D;T
Polyphen
D;D;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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