16-84313079-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021197.4(WFDC1):āc.263A>Cā(p.Glu88Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000157 in 1,271,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000016 ( 0 hom. )
Consequence
WFDC1
NM_021197.4 missense
NM_021197.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
WFDC1 (HGNC:15466): (WAP four-disulfide core domain 1) This gene encodes a member of the WAP-type four disulfide core domain family. The WAP-type four-disulfide core domain contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is mapped to chromosome 16q24, an area of frequent loss of heterozygosity in cancers, including prostate, breast and hepatocellular cancers and Wilms' tumor. This gene is downregulated in many cancer types and may be involved in the inhibition of cell proliferation. The encoded protein may also play a role in the susceptibility of certain CD4 memory T cells to human immunodeficiency virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35007393).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFDC1 | NM_021197.4 | c.263A>C | p.Glu88Ala | missense_variant | 2/7 | ENST00000219454.10 | NP_067020.2 | |
WFDC1 | NM_001282466.2 | c.263A>C | p.Glu88Ala | missense_variant | 2/7 | NP_001269395.1 | ||
WFDC1 | NM_001282467.2 | c.263A>C | p.Glu88Ala | missense_variant | 2/7 | NP_001269396.1 | ||
WFDC1 | XM_047434411.1 | c.263A>C | p.Glu88Ala | missense_variant | 2/6 | XP_047290367.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000157 AC: 2AN: 1271988Hom.: 0 Cov.: 30 AF XY: 0.00000160 AC XY: 1AN XY: 625286
GnomAD4 exome
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2
AN:
1271988
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Cov.:
30
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1
AN XY:
625286
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2024 | The c.263A>C (p.E88A) alteration is located in exon 2 (coding exon 2) of the WFDC1 gene. This alteration results from a A to C substitution at nucleotide position 263, causing the glutamic acid (E) at amino acid position 88 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of MoRF binding (P = 0.0607);Gain of MoRF binding (P = 0.0607);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at