chr1-22120073-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_030761.5(WNT4):c.1033G>A(p.Val345Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,601,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

WNT4
NM_030761.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Publications

2 publications found

Variant links:

Genes affected

WNT4 (HGNC:12783): (Wnt family member 4) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family, and is the first signaling molecule shown to influence the sex-determination cascade. It encodes a protein which shows 98% amino acid identity to the Wnt4 protein of mouse and rat. This gene and a nuclear receptor known to antagonize the testis-determining factor play a concerted role in both the control of female development and the prevention of testes formation. This gene and another two family members, WNT2 and WNT7B, may be associated with abnormal proliferation in breast tissue. Mutations in this gene can result in Rokitansky-Kuster-Hauser syndrome and in SERKAL syndrome. [provided by RefSeq, Jul 2008]

WNT4 Gene-Disease associations (from GenCC):

mullerian aplasia and hyperandrogenism
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
SERKAL syndrome
Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

WNT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030761.5. 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
	WNT4	NM_030761.5	MANE Select	c.1033G>A	p.Val345Met	missense	Exon 5 of 5	NP_110388.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT4	ENST00000290167.11	TSL:1 MANE Select	c.1033G>A	p.Val345Met	missense	Exon 5 of 5	ENSP00000290167.5	P56705-1
WNT4	ENST00000951124.1		c.991G>A	p.Val331Met	missense	Exon 5 of 5	ENSP00000621183.1
WNT4	ENST00000901549.1		c.934G>A	p.Val312Met	missense	Exon 5 of 5	ENSP00000571608.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000484

AC:

AN:

227262

AF XY:

0.0000480

show subpopulations

Gnomad AFR exome

AF:

0.0000720

Gnomad AMR exome

AF:

0.0000620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000487

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1449380

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

720972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33138

American (AMR)

AF:

0.0000694

AC:

AN:

43222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26040

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38640

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5444

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1109418

Other (OTH)

AF:

0.0000167

AC:

AN:

59932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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

AF:

0.0000197

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Genome 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

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000495

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.73

MetaSVM

Uncertain

0.43

MutationAssessor

Uncertain

2.8

PhyloP100

2.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.63

Sift

Uncertain

0.023

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.49

MutPred

0.54

Gain of disorder (P = 0.0615)

MVP

0.98

MPC

1.4

ClinPred

0.47

GERP RS

4.2

Varity_R

0.51

gMVP

0.88

Mutation Taster

=29/71

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over