16-84294987-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021197.4(WFDC1):c.16G>A(p.Val6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,613,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

WFDC1
NM_021197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.69

Publications

2 publications found

Variant links:

Genes affected

WFDC1 (HGNC:15466): (WAP four-disulfide core domain 1) This gene encodes a member of the WAP-type four disulfide core domain family. The WAP-type four-disulfide core domain contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is mapped to chromosome 16q24, an area of frequent loss of heterozygosity in cancers, including prostate, breast and hepatocellular cancers and Wilms' tumor. This gene is downregulated in many cancer types and may be involved in the inhibition of cell proliferation. The encoded protein may also play a role in the susceptibility of certain CD4 memory T cells to human immunodeficiency virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

WFDC1 links:

LOC124903734 (HGNC:):

LOC124903734 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.02744016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC1	NM_021197.4 link	c.16G>A	p.Val6Met	missense_variant	Exon 1 of 7	ENST00000219454.10	NP_067020.2	Q9HC57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WFDC1	ENST00000219454.10 link	c.16G>A	p.Val6Met	missense_variant	Exon 1 of 7	1	NM_021197.4	ENSP00000219454.5	Q9HC57
WFDC1	ENST00000568638.1 link	c.16G>A	p.Val6Met	missense_variant	Exon 1 of 7	2		ENSP00000456920.1	Q9HC57
WFDC1	ENST00000613603.1 link	c.16G>A	p.Val6Met	missense_variant	Exon 1 of 1	6		ENSP00000481580.1	A0A087WY77

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000152

AC:

AN:

250586

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000190

AC:

277

AN:

1461338

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726932

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33470

American (AMR)

AF:

0.000134

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000192

AC:

213

AN:

1111766

Other (OTH)

AF:

0.000248

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000236

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.000651

AC:

AN:

41470

American (AMR)

AF:

0.000196

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000289

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 17, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.16G>A (p.V6M) alteration is located in exon 1 (coding exon 1) of the WFDC1 gene. This alteration results from a G to A substitution at nucleotide position 16, causing the valine (V) at amino acid position 6 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.5

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.023

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.56

.;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;.

PhyloP100

-1.7

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.020

N;N;.

REVEL

Benign

0.022

Sift

Benign

0.095

T;T;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.31

B;B;.

Vest4

0.12

MVP

0.014

MPC

0.021

ClinPred

0.0091

GERP RS

-8.2

PromoterAI

-0.077

Neutral

(source)

Varity_R

0.030

gMVP

0.38

Mutation Taster

=97/3

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over