Variant 20-45110769-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145652.4(WFDC5):c.92C>G(p.Ser31Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WFDC5
NM_145652.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3014129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC5	NM_145652.4 linkuse as main transcript	c.92C>G	p.Ser31Trp	missense_variant	2/4	ENST00000372789.6	NP_663627.1	Q8TCV5-2
WFDC5	NM_001395506.1 linkuse as main transcript	c.92C>G	p.Ser31Trp	missense_variant	4/6		NP_001382435.1
WFDC5	XM_047439930.1 linkuse as main transcript	c.98C>G	p.Ser33Trp	missense_variant	1/3		XP_047295886.1
WFDC5	XM_011528601.2 linkuse as main transcript	c.92C>G	p.Ser31Trp	missense_variant	3/5		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.92C>G	p.Ser31Trp	missense_variant	2/4	1	NM_145652.4	ENSP00000361875.4		Q8TCV5-2
WFDC5	ENST00000307971.7 linkuse as main transcript	c.92C>G	p.Ser31Trp	missense_variant	2/4	5		ENSP00000312381.4		Q8TCV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250218

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135314

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727084

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:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

2.5

DANN

Benign

0.94

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.24

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.20

Sift

Benign

0.16

T;T

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;.

Vest4

0.30

MutPred

0.43

Loss of glycosylation at S31 (P = 0.003);Loss of glycosylation at S31 (P = 0.003);

MVP

0.17

MPC

0.27

ClinPred

0.40

GERP RS

-2.9

Varity_R

0.064

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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