20-45124380-C-T

Variant names:

• chr20-45124380-C-T
• rs1223365187
• NM_080869.2:c.68G>A

Variant summary

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

The NM_080869.2(WFDC12):​c.68G>A​(p.Gly23Glu) 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. 14/22 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. G23V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WFDC12 NM_080869.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 0 publications found

Genes affected

WFDC12 (HGNC:16115): (WAP four-disulfide core domain 12) 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 centromeric cluster. [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=0.17474768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080869.2. 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
	WFDC12	NM_080869.2	MANE Select	c.68G>A	p.Gly23Glu	missense	Exon 1 of 3	NP_543145.1	Q8WWY7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC12	ENST00000372785.3	TSL:1 MANE Select	c.68G>A	p.Gly23Glu	missense	Exon 1 of 3	ENSP00000361871.3	Q8WWY7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.38
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.058
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.86	P
Vest4		0.16
MutPred		0.54		Loss of ubiquitination at K25 (P = 0.1166)
MVP		0.055
MPC		0.13
ClinPred		0.61	D
GERP RS		-0.51
PromoterAI		0.036	Neutral
Varity_R		0.21
gMVP		0.44
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: rs1223365187; hg19: chr20-43753021;