chr1-44649887-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018150.4(RNF220):c.1559C>T(p.Ser520Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
RNF220
NM_018150.4 missense
NM_018150.4 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 7.56
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF220 | NM_018150.4 | c.1559C>T | p.Ser520Leu | missense_variant | 14/15 | ENST00000361799.7 | NP_060620.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF220 | ENST00000361799.7 | c.1559C>T | p.Ser520Leu | missense_variant | 14/15 | 1 | NM_018150.4 | ENSP00000354872 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251378Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135856
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461804Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727206
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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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 | Dec 11, 2023 | The c.1559C>T (p.S520L) alteration is located in exon 14 (coding exon 13) of the RNF220 gene. This alteration results from a C to T substitution at nucleotide position 1559, causing the serine (S) at amino acid position 520 to be replaced by a leucine (L). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;.
Vest4
MutPred
Loss of catalytic residue at S520 (P = 0.026);Loss of catalytic residue at S520 (P = 0.026);Loss of catalytic residue at S520 (P = 0.026);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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