20-45538029-C-T

Variant names:

• chr20-45538029-C-T
• rs199553388
• NM_080827.2:c.157G>A

Variant summary

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

The NM_080827.2(WFDC6):​c.157G>A​(p.Asp53Asn) 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. 15/21 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. D53Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WFDC6 NM_080827.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 1 publications found

Genes affected

WFDC6 (HGNC:16164): (WAP four-disulfide core domain 6) 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. Read-through transcription exists between this gene and the upstream SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) gene. [provided by RefSeq, Nov 2010]

EPPIN-WFDC6 (HGNC:38825): (EPPIN-WFDC6 readthrough) This locus represents naturally occurring read-through transcription between the neighboring SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) and WFDC6 (WAP four-disulfide core domain 6) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

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=0.13531196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080827.2. 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
	WFDC6	NM_080827.2	MANE Select	c.157G>A	p.Asp53Asn	missense	Exon 2 of 3	NP_543017.1	Q9BQY6-2
	EPPIN-WFDC6	NM_001198986.2		c.457G>A	p.Asp153Asn	missense	Exon 4 of 5	NP_001185915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC6	ENST00000372670.8	TSL:1 MANE Select	c.157G>A	p.Asp53Asn	missense	Exon 2 of 3	ENSP00000361755.3	Q9BQY6-2
	EPPIN-WFDC6	ENST00000651288.1		c.457G>A	p.Asp153Asn	missense	Exon 4 of 5	ENSP00000498632.1	A0A494C0M2
	EPPIN-WFDC6	ENST00000504988.1	TSL:2	c.457G>A	p.Asp153Asn	missense	Exon 4 of 5	ENSP00000424176.1	O95925-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	-0.56
CADD	Benign	9.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.88	T
PhyloP100		-0.18
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.065
Sift	Benign	0.054	T
Sift4G	Benign	0.098	T
Polyphen		0.40	B
Vest4		0.21
MutPred		0.45		Gain of catalytic residue at D153 (P = 0.0193)
MVP		0.46
MPC		0.22
ClinPred		0.10	T
GERP RS		0.11
Varity_R		0.024
gMVP		0.39
Mutation Taster		=100/0	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: rs199553388; hg19: chr20-44166668;