20-45684928-C-A

Position:

• chr20-45684928-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172006.2(WFDC10B):​c.124G>T​(p.Asp42Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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: 31)
• Consequence: WFDC10B NM_172006.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.10

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060418516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC10B	NM_172006.2	c.124G>T	p.Asp42Tyr	missense_variant	4/4	ENST00000330523.10	NP_742003.1
WFDC10B	NM_172131.2	c.172G>T	p.Asp58Tyr	missense_variant	3/3		NP_742143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC10B	ENST00000330523.10	c.124G>T	p.Asp42Tyr	missense_variant	4/4	1	NM_172006.2	ENSP00000327628.5
WFDC10B	ENST00000335769.2	c.172G>T	p.Asp58Tyr	missense_variant	3/3	1		ENSP00000337466.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.172G>T (p.D58Y) alteration is located in exon 3 (coding exon 3) of the WFDC10B gene. This alteration results from a G to T substitution at nucleotide position 172, causing the aspartic acid (D) at amino acid position 58 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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0030
DANN	Benign	0.10
DEOGEN2	Benign	0.0019	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.028
Sift	Benign	0.31	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.15
MutPred		0.38		Gain of sheet (P = 0.0061);.;
MVP		0.030
MPC		0.071
ClinPred		0.083	T
GERP RS		-7.5
Varity_R		0.050
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44313567;