chr20-45538029-C-A

Position:

chr20-45538029-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080827.2(WFDC6):c.157G>T(p.Asp53Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

WFDC6
NM_080827.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

Variant links:

Genes affected

WFDC6 (HGNC:16164): (WAP four-disulfide core domain 6) This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Read-through transcription exists between this gene and the upstream SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) gene. [provided by RefSeq, Nov 2010]

WFDC6 links:

EPPIN-WFDC6 (HGNC:38825): (EPPIN-WFDC6 readthrough) This locus represents naturally occurring read-through transcription between the neighboring SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) and WFDC6 (WAP four-disulfide core domain 6) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

EPPIN-WFDC6 links:

ENSG00000291238 (HGNC:):

ENSG00000291238 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15032509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC6	NM_080827.2 link	c.157G>T	p.Asp53Tyr	missense_variant	2/3	ENST00000372670.8	NP_543017.1	Q9BQY6-2A0A0K0K1K0
EPPIN-WFDC6	NM_001198986.2 link	c.457G>T	p.Asp153Tyr	missense_variant	4/5		NP_001185915.1	O95925-3
LOC107987282	XR_001754641.3 link	n.153-507C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WFDC6	ENST00000372670.8 link	c.157G>T	p.Asp53Tyr	missense_variant	2/3	1	NM_080827.2	ENSP00000361755.3	Q9BQY6-2
EPPIN-WFDC6	ENST00000651288.1 link	c.457G>T	p.Asp153Tyr	missense_variant	4/5			ENSP00000498632.1	A0A494C0M2
EPPIN-WFDC6	ENST00000504988.1 link	c.457G>T	p.Asp153Tyr	missense_variant	4/5	2		ENSP00000424176.1	O95925-3
ENSG00000291238	ENST00000372665.4 link	n.157G>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251322

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135820

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:

0.000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727188

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:

0.0000374

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000105

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.457G>T (p.D153Y) alteration is located in exon 4 (coding exon 4) of the EPPIN-WFDC6 gene. This alteration results from a G to T substitution at nucleotide position 457, causing the aspartic acid (D) at amino acid position 153 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.58

.;D;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.82

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

N;N;D

REVEL

Benign

0.17

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.022

D;.;T

Polyphen

0.85

P;.;.

Vest4

0.32

MVP

0.31

MPC

0.30

ClinPred

0.14

GERP RS

0.11

Varity_R

0.028

gMVP

0.61

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over