rs138817814

Variant names:

• chr20-45538052-A-C
• rs138817814
• NM_080827.2:c.134T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45538052-A-C
• chr20-45538052-A-G
• chr20-45538052-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080827.2(WFDC6):​c.134T>G​(p.Ile45Arg) 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. 13/19 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. I45T) 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: -1.42

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]

ENSG00000291238 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031443298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC6	NM_080827.2	c.134T>G	p.Ile45Arg	missense_variant	Exon 2 of 3	ENST00000372670.8	NP_543017.1
EPPIN-WFDC6	NM_001198986.2	c.434T>G	p.Ile145Arg	missense_variant	Exon 4 of 5		NP_001185915.1
LOC107987282	XR_001754641.3	n.153-484A>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFDC6	ENST00000372670.8	c.134T>G	p.Ile45Arg	missense_variant	Exon 2 of 3	1	NM_080827.2	ENSP00000361755.3
EPPIN-WFDC6	ENST00000651288.1	c.434T>G	p.Ile145Arg	missense_variant	Exon 4 of 5			ENSP00000498632.1
EPPIN-WFDC6	ENST00000504988.1	c.434T>G	p.Ile145Arg	missense_variant	Exon 4 of 5	2		ENSP00000424176.1
ENSG00000291238	ENST00000372665.4	n.134T>G		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.30
DANN	Benign	0.34
DEOGEN2	Benign	0.095	.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.25	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-0.64	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	4.5	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.76	T;T;T
Sift4G	Benign	0.90	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.25
MutPred		0.34		.;.;Gain of solvent accessibility (P = 0.0039);
MVP		0.14
MPC		0.085
ClinPred		0.035	T
GERP RS		-5.8
Varity_R		0.035
gMVP		0.35

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: rs138817814; hg19: chr20-44166691;