Variant 20-45110427-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145652.4(WFDC5):c.340G>A(p.Gly114Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,610,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

WFDC5
NM_145652.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

WFDC5 (HGNC:20477): (WAP four-disulfide core domain 5) This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. Most WFDC proteins contain only one WFDC domain, and this encoded protein contains two WFDC domains. 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 centromeric cluster. [provided by RefSeq, Jul 2008]

WFDC5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC5	NM_145652.4 linkuse as main transcript	c.340G>A	p.Gly114Arg	missense_variant	3/4	ENST00000372789.6	NP_663627.1	Q8TCV5-2
WFDC5	NM_001395506.1 linkuse as main transcript	c.340G>A	p.Gly114Arg	missense_variant	5/6		NP_001382435.1
WFDC5	XM_047439930.1 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	2/3		XP_047295886.1
WFDC5	XM_011528601.2 linkuse as main transcript	c.340G>A	p.Gly114Arg	missense_variant	4/5		XP_011526903.1	Q8TCV5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC5	ENST00000372789.6 linkuse as main transcript	c.340G>A	p.Gly114Arg	missense_variant	3/4	1	NM_145652.4	ENSP00000361875.4		Q8TCV5-2
WFDC5	ENST00000307971.7 linkuse as main transcript	c.340G>A	p.Gly114Arg	missense_variant	3/4	5		ENSP00000312381.4		Q8TCV5-1

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

240802

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

130434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000674

Gnomad FIN exome

AF:

0.0000494

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

169

AN:

1457922

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

102

AN XY:

724870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000431

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000190

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000124

AC:

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

Oct 03, 2023

The c.340G>A (p.G114R) alteration is located in exon 3 (coding exon 3) of the WFDC5 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the glycine (G) at amino acid position 114 to be replaced by an arginine (R). 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

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

0.0088

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.7

D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.44

MutPred

0.84

Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);

MVP

0.82

MPC

0.72

ClinPred

0.84

GERP RS

5.1

Varity_R

0.53

gMVP

0.76

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