chr20-45788963-C-G

Variant names:

• chr20-45788963-C-G
• NM_080614.2:c.179G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080614.2(WFDC3):​c.179G>C​(p.Gly60Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WFDC3 NM_080614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30002803).

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.179G>C	p.Gly60Ala	missense	Exon 3 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.179G>C	p.Gly60Ala	missense	Exon 3 of 7	ENSP00000243938.4	Q8IUB2
	WFDC3	ENST00000337205.8	TSL:1	c.158G>C	p.Gly53Ala	missense	Exon 3 of 7	ENSP00000337815.4	H0Y2V5
	WFDC3	ENST00000487343.5	TSL:1	n.169G>C		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.56		Gain of MoRF binding (P = 0.1123)
MVP		0.26
MPC		0.44
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.64
gMVP		0.71
Mutation Taster		=93/7	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

hg19: chr20-44417602;