20-45650546-C-T

Variant names:

• chr20-45650546-C-T
• NM_147197.2:c.55G>A

Variant summary

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

The NM_147197.2(WFDC11):​c.55G>A​(p.Val19Met) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WFDC11 NM_147197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.319
• Publications: 0 publications found

Genes affected

WFDC11 (HGNC:20478): (WAP four-disulfide core domain 11) 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. [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=0.2686537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147197.2. 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
	WFDC11	NM_147197.2	MANE Select	c.55G>A	p.Val19Met	missense	Exon 3 of 5	NP_671730.1	Q8NEX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC11	ENST00000324384.4	TSL:1 MANE Select	c.55G>A	p.Val19Met	missense	Exon 3 of 5	ENSP00000318753.3	Q8NEX6
	WFDC11	ENST00000356562.6	TSL:1	c.55G>A	p.Val19Met	missense	Exon 3 of 5	ENSP00000348968.2	Q8NEX6
	WFDC11	ENST00000618797.4	TSL:5	c.55G>A	p.Val19Met	missense	Exon 2 of 4	ENSP00000479579.1	Q8NEX6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.089
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.32
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.037
Sift	Benign	0.13	T
Sift4G	Benign	0.093	T
Polyphen		0.98	D
Vest4		0.14
MutPred		0.30		Gain of MoRF binding (P = 0.1447)
MVP		0.014
MPC		0.050
ClinPred		0.58	D
GERP RS		0.11
Varity_R		0.024
gMVP		0.21
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

hg19: chr20-44279185; COSMIC: COSV60976424;