NM_080614.2:c.106C>G

Variant names:

• chr20-45789036-G-C
• rs6032538
• NM_080614.2:c.106C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080614.2(WFDC3):​c.106C>G​(p.His36Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,612,010 control chromosomes in the GnomAD database, including 406,684 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37068 hom., cov: 31)
  • Exomes 𝑓: 0.71 (369616 hom.)
• Consequence: WFDC3 NM_080614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 34 publications found

Genes affected

WFDC3 (HGNC:15957): (WAP four-disulfide core domain 3) 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 four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.755524E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080614.2. 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
	WFDC3	NM_080614.2	MANE Select	c.106C>G	p.His36Asp	missense	Exon 3 of 7	NP_542181.1	Q8IUB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC3	ENST00000243938.9	TSL:1 MANE Select	c.106C>G	p.His36Asp	missense	Exon 3 of 7	ENSP00000243938.4	Q8IUB2
	WFDC3	ENST00000337205.8	TSL:1	c.85C>G	p.His29Asp	missense	Exon 3 of 7	ENSP00000337815.4	H0Y2V5
	WFDC3	ENST00000487343.5	TSL:1	n.96C>G		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105730 AN: 151884 Hom.: 37043 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.693 AC: 173085 AN: 249660 AF XY: 0.683

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.588

Gnomad EAS exome AF: 0.617

Gnomad FIN exome AF: 0.688

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.710 AC: 1036145 AN: 1460008 Hom.: 369616 Cov.: 60 AF XY: 0.704 AC XY: 511486 AN XY: 726292

African (AFR) AF: 0.652 AC: 21749 AN: 33348

American (AMR) AF: 0.816 AC: 36088 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 15597 AN: 26054

East Asian (EAS) AF: 0.667 AC: 26406 AN: 39588

South Asian (SAS) AF: 0.568 AC: 48777 AN: 85910

European-Finnish (FIN) AF: 0.698 AC: 37262 AN: 53394

Middle Eastern (MID) AF: 0.619 AC: 3567 AN: 5760

European-Non Finnish (NFE) AF: 0.725 AC: 805296 AN: 1111420

Other (OTH) AF: 0.686 AC: 41403 AN: 60320

GnomAD4 genome AF: 0.696 AC: 105806 AN: 152002 Hom.: 37068 Cov.: 31 AF XY: 0.693 AC XY: 51446 AN XY: 74286

African (AFR) AF: 0.661 AC: 27393 AN: 41456

American (AMR) AF: 0.762 AC: 11636 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2133 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3233 AN: 5160

South Asian (SAS) AF: 0.568 AC: 2729 AN: 4802

European-Finnish (FIN) AF: 0.696 AC: 7347 AN: 10558

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48935 AN: 67966

Other (OTH) AF: 0.687 AC: 1451 AN: 2112

Alfa AF: 0.698 Hom.: 25672

Bravo AF: 0.702

TwinsUK AF: 0.717 AC: 2657

ALSPAC AF: 0.725 AC: 2794

ESP6500AA AF: 0.665 AC: 2929

ESP6500EA AF: 0.714 AC: 6139

ExAC AF: 0.689 AC: 83605

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.0
DANN	Benign	0.74
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000070	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	6.8e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-3.2	N
PhyloP100		-0.15
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.094
Sift	Benign	0.87	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.079
MPC		0.12
ClinPred		0.0023	T
GERP RS		1.1
Varity_R		0.11
gMVP		0.56
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs6032538; hg19: chr20-44417675; COSMIC: COSV54786488; COSMIC: COSV54786488;