16-631414-G-T

Variant names:

• chr16-631414-G-T
• rs138836137
• NM_053284.3:c.161G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053284.3(WFIKKN1):​c.161G>T​(p.Ser54Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,608,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. S54N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: WFIKKN1 NM_053284.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047112405).

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.161G>T	p.Ser54Ile	missense	Exon 1 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.161G>T	p.Ser54Ile	missense	Exon 1 of 2	ENSP00000324763.2	Q96NZ8
	WFIKKN1	ENST00000573440.1	TSL:6	n.2176G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000245 AC: 60 AN: 244642 AF XY: 0.000150

Gnomad AFR exome AF: 0.00378

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000892 AC: 130 AN: 1456614 Hom.: 0 Cov.: 33 AF XY: 0.0000704 AC XY: 51 AN XY: 724836

African (AFR) AF: 0.00349 AC: 116 AN: 33238

American (AMR) AF: 0.0000896 AC: 4 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111146

Other (OTH) AF: 0.000166 AC: 10 AN: 60266

GnomAD4 genome AF: 0.000907 AC: 138 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000860 AC XY: 64 AN XY: 74404

African (AFR) AF: 0.00325 AC: 135 AN: 41516

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000558 Hom.: 0

Bravo AF: 0.00101

ESP6500AA AF: 0.00387 AC: 17

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000281 AC: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.0
DANN	Benign	0.86
DEOGEN2	Benign	0.094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.22
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Benign	0.065	T
Polyphen		0.0040	B
Vest4		0.12
MVP		0.35
MPC		0.14
ClinPred		0.0033	T
GERP RS		-2.5
PromoterAI		-0.00080	Neutral
Varity_R		0.15
gMVP		0.24
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs138836137; hg19: chr16-681414;