chr20-45552040-C-G

Variant names:

• chr20-45552040-C-G
• rs1980051713
• NM_130896.3:c.712G>C

Variant summary

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

The NM_130896.3(WFDC8):​c.712G>C​(p.Asp238His) 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: WFDC8 NM_130896.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.306
• Publications: 0 publications found

Genes affected

WFDC8 (HGNC:16163): (WAP four-disulfide core domain 8) 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 a Kunitz-inhibitor domain, in addition to three WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Two alternatively spliced transcript variants have been found for this gene, and they encode the same protein. [provided by RefSeq, Jul 2008]

ENSG00000237464 (HGNC:):

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=0.22271028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130896.3. 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
	WFDC8	NM_130896.3	MANE Select	c.712G>C	p.Asp238His	missense	Exon 6 of 6	NP_570966.2	Q8IUA0
	WFDC8	NM_181510.3		c.712G>C	p.Asp238His	missense	Exon 6 of 7	NP_852611.2	A0A140VK68

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC8	ENST00000289953.3	TSL:1 MANE Select	c.712G>C	p.Asp238His	missense	Exon 6 of 6	ENSP00000289953.2	Q8IUA0
	WFDC8	ENST00000357199.8	TSL:1	c.712G>C	p.Asp238His	missense	Exon 6 of 7	ENSP00000361735.3	Q8IUA0
	ENSG00000237464	ENST00000803561.1		n.520-4315C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.3
DANN	Benign	0.47
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.31
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Uncertain	0.013	D
Polyphen		0.74	P
Vest4		0.14
MutPred		0.39		Loss of ubiquitination at K235 (P = 0.0228)
MVP		0.41
MPC		0.16
ClinPred		0.33	T
GERP RS		-3.4
Varity_R		0.038
gMVP		0.35
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1980051713; hg19: chr20-44180679; COSMIC: COSV51489247; COSMIC: COSV51489247;