Genetic Variant WWP1:p.Asp190His (chr8-86402047-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_007013.4(WWP1):c.568G>C(p.Asp190His) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,454,518 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D190N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WWP1
NM_007013.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.75

Publications

0 publications found

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]

WWP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWP1	NM_007013.4	MANE Select	c.568G>C	p.Asp190His	missense	Exon 8 of 25	NP_008944.1	Q9H0M0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WWP1	ENST00000517970.6	TSL:1 MANE Select	c.568G>C	p.Asp190His	missense	Exon 8 of 25	ENSP00000427793.1	Q9H0M0-1
WWP1	ENST00000265428.4	TSL:1	c.568G>C	p.Asp190His	missense	Exon 6 of 23	ENSP00000265428.4	Q9H0M0-1
WWP1	ENST00000518683.5	TSL:1	n.378+3409G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1454518

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33034

American (AMR)

AF:

0.00

AC:

AN:

43922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25920

East Asian (EAS)

AF:

0.00

AC:

AN:

39108

South Asian (SAS)

AF:

0.0000703

AC:

AN:

85330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108194

Other (OTH)

AF:

0.00

AC:

AN:

60010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.81

PhyloP100

6.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

REVEL

Benign

0.20

Sift

Benign

0.032

Sift4G

Benign

0.10

Polyphen

0.90

Vest4

0.69

MutPred

0.26

Loss of catalytic residue at D190 (P = 0.0453)

MVP

0.082

MPC

0.45

ClinPred

0.69

GERP RS

5.7

Varity_R

0.079

gMVP

0.39

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over