rs6032538

Positions:

• chr20-45789036-G-A
• chr20-45789036-G-C
• chr20-45789036-G-T

Variant summary

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

The NM_080614.2(WFDC3):​c.106C>T​(p.His36Tyr) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H36D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WFDC3 NM_080614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

WFDC3 (HGNC:15957): (WAP four-disulfide core domain 3) 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. The encoded protein contains four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined. [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=0.042435706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WFDC3	NM_080614.2	c.106C>T	p.His36Tyr	missense_variant	3/7	ENST00000243938.9
WFDC3	XM_011528553.3	c.124C>T	p.His42Tyr	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WFDC3	ENST00000243938.9	c.106C>T	p.His36Tyr	missense_variant	3/7	1	NM_080614.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460974 Hom.: 0 Cov.: 60 AF XY: 0.00 AC XY: 0 AN XY: 726808

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.81	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.35	N;N
REVEL	Benign	0.046
Sift	Benign	1.0	T;D
Sift4G	Benign	0.56	T;T
Polyphen		0.0020	B;.
Vest4		0.13
MutPred		0.41		Gain of phosphorylation at H36 (P = 0.112);Gain of phosphorylation at H36 (P = 0.112);
MVP		0.28
MPC		0.10
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.054
gMVP		0.43

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

Other links and lift over

dbSNP: rs6032538; hg19: chr20-44417675;