Variant chr20-45684949-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_172006.2(WFDC10B):c.103T>C(p.Cys35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WFDC10B
NM_172006.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

WFDC10B (HGNC:20479): (WAP four-disulfide core domain 10B) 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. Two alternatively spliced transcript variants have been found for this gene, and they encode distinct isoforms. [provided by RefSeq, Jul 2008]

WFDC10B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC10B	NM_172006.2 linkuse as main transcript	c.103T>C	p.Cys35Arg	missense_variant	4/4	ENST00000330523.10	NP_742003.1	Q8IUB3-1
WFDC10B	NM_172131.2 linkuse as main transcript	c.151T>C	p.Cys51Arg	missense_variant	3/3		NP_742143.1	Q8IUB3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC10B	ENST00000330523.10 linkuse as main transcript	c.103T>C	p.Cys35Arg	missense_variant	4/4	1	NM_172006.2	ENSP00000327628.5		Q8IUB3-1
WFDC10B	ENST00000335769.2 linkuse as main transcript	c.151T>C	p.Cys51Arg	missense_variant	3/3	1		ENSP00000337466.2		Q8IUB3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251070

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Sep 22, 2023

The c.151T>C (p.C51R) alteration is located in exon 3 (coding exon 3) of the WFDC10B gene. This alteration results from a T to C substitution at nucleotide position 151, causing the cysteine (C) at amino acid position 51 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

0.77

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.48

T;T

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.29

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-10

D;D

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.94

MutPred

0.48

Gain of disorder (P = 0.002);.;

MVP

0.56

MPC

0.47

ClinPred

0.99

GERP RS

3.8

Varity_R

0.74

gMVP

0.50

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