20-45787852-G-C

Variant names:

• chr20-45787852-G-C
• rs1601017951
• NM_080614.2:c.342C>G

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.342C>G​(p.Ile114Met) 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. 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: 0.491
• 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=0.089454144).

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.342C>G	p.Ile114Met	missense	Exon 4 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.342C>G	p.Ile114Met	missense	Exon 4 of 7	ENSP00000243938.4	Q8IUB2
	WFDC3	ENST00000337205.8	TSL:1	c.321C>G	p.Ile107Met	missense	Exon 4 of 7	ENSP00000337815.4	H0Y2V5
	WFDC3	ENST00000462017.5	TSL:1	n.203C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.092
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.5
DANN	Benign	0.70
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.49
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.092
Sift	Benign	0.12	T
Sift4G	Benign	0.26	T
Polyphen		0.38	B
Vest4		0.11
MutPred		0.17		Loss of catalytic residue at L119 (P = 0.0498)
MVP		0.48
MPC		0.089
ClinPred		0.067	T
GERP RS		1.1
Varity_R		0.053
gMVP		0.40
Mutation Taster		=97/3	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: rs1601017951; hg19: chr20-44416491; COSMIC: COSV54786719; COSMIC: COSV54786719;