16-632751-G-C

Position:

• chr16-632751-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_053284.3(WFIKKN1):​c.341G>C​(p.Cys114Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: WFIKKN1 NM_053284.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

Genes affected

WFIKKN1 (HGNC:30912): (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 1) This gene encodes a secreted multidomain protein consisting of a signal peptide, a WAP domain, a follistatin domain, an immunoglobulin domain, two tandem Kunitz domains, and an NTR domain. These domains have been implicated frequently in inhibition of various types of proteases, suggesting that the encoded protein may be a multivalent protease inhibitor and may control the action of multiple types of serine proteases as well as metalloproteinases. [provided by RefSeq, Jul 2008]

WFIKKN1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFIKKN1	NM_053284.3	c.341G>C	p.Cys114Ser	missense_variant	2/2	ENST00000319070.3	NP_444514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFIKKN1	ENST00000319070.3	c.341G>C	p.Cys114Ser	missense_variant	2/2	1	NM_053284.3	ENSP00000324763.2
WFIKKN1	ENST00000573440.1	n.3513G>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.341G>C (p.C114S) alteration is located in exon 2 (coding exon 2) of the WFIKKN1 gene. This alteration results from a G to C substitution at nucleotide position 341, causing the cysteine (C) at amino acid position 114 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.59		Gain of glycosylation at C114 (P = 0.0101);
MVP		0.51
MPC		0.61
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.90
gMVP		0.89

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: chr16-682751;