rs1333977438

Variant names:

• chr20-45775558-C-A
• rs1333977438
• NM_080614.2:c.538G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-45775558-C-A
• chr20-45775558-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080614.2(WFDC3):​c.538G>T​(p.Val180Phe) 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. 17/22 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. V180I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: WFDC3 NM_080614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16867712).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080614.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC3	NM_080614.2	MANE Select	c.538G>T	p.Val180Phe	missense	Exon 6 of 7	NP_542181.1	Q8IUB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC3	ENST00000243938.9	TSL:1 MANE Select	c.538G>T	p.Val180Phe	missense	Exon 6 of 7	ENSP00000243938.4	Q8IUB2
	WFDC3	ENST00000337205.8	TSL:1	c.517G>T	p.Val173Phe	missense	Exon 6 of 7	ENSP00000337815.4	H0Y2V5
	WFDC3	ENST00000462017.5	TSL:1	n.264G>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.17
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.17	T
Sift4G	Benign	0.32	T
Polyphen		0.61	P
Vest4		0.48
MutPred		0.59		Loss of stability (P = 0.1331)
MVP		0.42
MPC		0.44
ClinPred		0.19	T
GERP RS		-0.88
Varity_R		0.039
gMVP		0.42
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1333977438; hg19: chr20-44404197;