Genetic Variant WFIKKN1:p.Ala90Val (chr16-632679-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053284.3(WFIKKN1):c.269C>T(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,453,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

WFIKKN1
NM_053284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.562

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054886997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053284.3. 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
	WFIKKN1	NM_053284.3	MANE Select	c.269C>T	p.Ala90Val	missense	Exon 2 of 2	NP_444514.1	Q96NZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFIKKN1	ENST00000319070.3	TSL:1 MANE Select	c.269C>T	p.Ala90Val	missense	Exon 2 of 2	ENSP00000324763.2	Q96NZ8
	WFIKKN1	ENST00000573440.1	TSL:6	n.3441C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

236302

AF XY:

0.00000775

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000173

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1453610

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722464

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33240

American (AMR)

AF:

0.00

AC:

AN:

44012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25928

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39330

South Asian (SAS)

AF:

0.00

AC:

AN:

85338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1108376

Other (OTH)

AF:

0.00

AC:

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000250

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.7

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.50

M_CAP

Benign

0.012

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.35

PhyloP100

-0.56

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

REVEL

Benign

0.035

Sift

Benign

0.25

Sift4G

Benign

0.18

Polyphen

0.0020

Vest4

0.080

MVP

0.43

MPC

0.11

ClinPred

0.036

GERP RS

2.1

Varity_R

0.035

gMVP

0.26

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over