rs201744082

Variant names:

• chr20-45555761-C-A
• rs201744082
• NM_130896.3:c.385G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-45555761-C-A
• chr20-45555761-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_130896.3(WFDC8):​c.385G>T​(p.Glu129*) variant causes a stop gained 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WFDC8 NM_130896.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.56

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC8	NM_130896.3	c.385G>T	p.Glu129*	stop_gained	Exon 4 of 6	ENST00000289953.3	NP_570966.2
WFDC8	NM_181510.3	c.385G>T	p.Glu129*	stop_gained	Exon 4 of 7		NP_852611.2
WFDC8	XM_017028119.2	c.385G>T	p.Glu129*	stop_gained	Exon 4 of 5		XP_016883608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFDC8	ENST00000289953.3	c.385G>T	p.Glu129*	stop_gained	Exon 4 of 6	1	NM_130896.3	ENSP00000289953.2
WFDC8	ENST00000357199.8	c.385G>T	p.Glu129*	stop_gained	Exon 4 of 7	1		ENSP00000361735.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152188 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Uncertain	24
DANN	Benign	0.65
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0046	N
Vest4		0.12
GERP RS		-8.5

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

Publications

LitVar

Other links and lift over

dbSNP: rs201744082; hg19: chr20-44184400;