chr8-86435486-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_StrongBP6_Moderate
The NM_007013.4(WWP1):c.1636G>A(p.Gly546Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
WWP1
NM_007013.4 missense
NM_007013.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 5.97
Genes affected
WWP1 (HGNC:17004): (WW domain containing E3 ubiquitin protein ligase 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, WWP1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05981359).
BP6
?
Variant 8-86435486-G-A is Benign according to our data. Variant chr8-86435486-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2354465.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WWP1 | NM_007013.4 | c.1636G>A | p.Gly546Ser | missense_variant | 15/25 | ENST00000517970.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WWP1 | ENST00000517970.6 | c.1636G>A | p.Gly546Ser | missense_variant | 15/25 | 1 | NM_007013.4 | P1 | |
WWP1 | ENST00000265428.4 | c.1636G>A | p.Gly546Ser | missense_variant | 13/23 | 1 | P1 | ||
WWP1 | ENST00000518683.5 | n.1290G>A | non_coding_transcript_exon_variant | 11/15 | 1 | ||||
WWP1 | ENST00000520453.5 | c.31G>A | p.Gly11Ser | missense_variant | 1/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251420Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727224
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at G546 (P = 0.0636);Gain of catalytic residue at G546 (P = 0.0636);
MVP
MPC
ClinPred
T
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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