rs773370868

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_007013.4(WWP1):ā€‹c.1879A>Gā€‹(p.Met627Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

WWP1
NM_007013.4 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.787
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WWP1NM_007013.4 linkc.1879A>G p.Met627Val missense_variant Exon 18 of 25 ENST00000517970.6 NP_008944.1 Q9H0M0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WWP1ENST00000517970.6 linkc.1879A>G p.Met627Val missense_variant Exon 18 of 25 1 NM_007013.4 ENSP00000427793.1 Q9H0M0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250322
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135336
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1458694
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
725646
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Benign
-0.33
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.8
D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.015
D;D
Polyphen
1.0
D;D
Vest4
0.73
MutPred
0.59
Loss of catalytic residue at M627 (P = 0.0076);Loss of catalytic residue at M627 (P = 0.0076);
MVP
0.47
MPC
2.0
ClinPred
0.96
D
GERP RS
5.4
Varity_R
0.88
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773370868; hg19: chr8-87454888; API