NM_080753.3:c.155A>G

Variant names:

Variant summary

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

The NM_080753.3(WFDC10A):c.155A>G(p.His52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. H52L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WFDC10A
NM_080753.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

0 publications found

Variant links:

Genes affected

WFDC10A (HGNC:16139): (WAP four-disulfide core domain 10A) 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]

WFDC10A links:

WFDC9 (HGNC:20380): (WAP four-disulfide core domain 9) The WAP-type four-disulfide core (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 in many members of the WFDC domain family. This gene encodes a protein which contains a WFDC domain, and is thus a member of the WFDC domain family. This gene and several other gene family members are clustered at 20q13.12. [provided by RefSeq, Jul 2008]

WFDC9 links:

Genome browser will be placed here

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=0.041086435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080753.3. 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
	WFDC10A	NM_080753.3	MANE Select	c.155A>G	p.His52Arg	missense	Exon 2 of 2	NP_542791.1	Q9H1F0
	WFDC9	NM_147198.4	MANE Select	c.-153+270T>C		intron	N/A	NP_671731.1	Q8NEX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC10A	ENST00000372643.4	TSL:1 MANE Select	c.155A>G	p.His52Arg	missense	Exon 2 of 2	ENSP00000361726.3	Q9H1F0
	WFDC9	ENST00000326000.2	TSL:1 MANE Select	c.-153+270T>C		intron	N/A	ENSP00000320532.1	Q8NEX5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

249392

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000200

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:

0.00000274

AC:

AN:

1460474

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111452

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.0000132

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0010

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00062

LIST_S2

Benign

0.21

M_CAP

Benign

0.0054

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.99

PhyloP100

-1.9

PrimateAI

Benign

0.26

PROVEAN

Benign

0.74

REVEL

Benign

0.058

Sift

Benign

1.0

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.050

MutPred

0.55

Loss of ubiquitination at K51 (P = 0.0356)

MVP

0.076

MPC

0.020

ClinPred

0.058

GERP RS

-1.1

PromoterAI

-0.0022

Neutral

(source)

Varity_R

0.025

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over