rs375904597

Variant names:

• chr20-45649339-T-C
• NM_147197.2:c.161A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-45649339-T-C
• chr20-45649339-T-G

Variant summary

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

The NM_147197.2(WFDC11):​c.161A>G​(p.Lys54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. K54T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: WFDC11 NM_147197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

WFDC11 (HGNC:20478): (WAP four-disulfide core domain 11) 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. [provided by RefSeq, Jul 2008]

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=0.030821592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC11	NM_147197.2	c.161A>G	p.Lys54Arg	missense_variant	Exon 4 of 5	ENST00000324384.4	NP_671730.1
WFDC11	XM_047440080.1	c.161A>G	p.Lys54Arg	missense_variant	Exon 4 of 5		XP_047296036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFDC11	ENST00000324384.4	c.161A>G	p.Lys54Arg	missense_variant	Exon 4 of 5	1	NM_147197.2	ENSP00000318753.3
WFDC11	ENST00000356562.6	c.161A>G	p.Lys54Arg	missense_variant	Exon 4 of 5	1		ENSP00000348968.2
WFDC11	ENST00000618797.4	c.161A>G	p.Lys54Arg	missense_variant	Exon 3 of 4	5		ENSP00000479579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.041
DANN	Benign	0.14
DEOGEN2	Benign	0.0037	T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.36	T;.;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.7	.;N;N
REVEL	Benign	0.0090
Sift	Benign	1.0	.;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.15	B;B;B
Vest4		0.15
MutPred		0.24		Loss of methylation at K54 (P = 0.007);Loss of methylation at K54 (P = 0.007);Loss of methylation at K54 (P = 0.007);
MVP		0.014
MPC		0.012
ClinPred		0.068	T
GERP RS		-3.9
Varity_R		0.023
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44277978;