NM_057168.2:c.778T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_057168.2(WNT16):c.778T>C(p.Ser260Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,614,040 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 6 hom. )

Consequence

WNT16
NM_057168.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.17

Publications

7 publications found

Variant links:

Genes affected

WNT16 (HGNC:16267): (Wnt family member 16) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

WNT16 links:

ENSG00000308687 (HGNC:):

ENSG00000308687 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00790751).

BP6

Variant 7-121339025-T-C is Benign according to our data. Variant chr7-121339025-T-C is described in ClinVar as Benign. ClinVar VariationId is 773396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00558 (849/152208) while in subpopulation AFR AF = 0.0186 (774/41526). AF 95% confidence interval is 0.0176. There are 9 homozygotes in GnomAd4. There are 392 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057168.2. 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
	WNT16	NM_057168.2	MANE Select	c.778T>C	p.Ser260Pro	missense	Exon 4 of 4	NP_476509.1	Q9UBV4-1
	WNT16	NM_016087.2		c.748T>C	p.Ser250Pro	missense	Exon 4 of 4	NP_057171.2	Q9UBV4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT16	ENST00000222462.3	TSL:1 MANE Select	c.778T>C	p.Ser260Pro	missense	Exon 4 of 4	ENSP00000222462.2	Q9UBV4-1
WNT16	ENST00000361301.6	TSL:1	c.748T>C	p.Ser250Pro	missense	Exon 4 of 4	ENSP00000355065.2	E9PH60
ENSG00000308687	ENST00000835700.1		n.189-57A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

849

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00159

AC:

399

AN:

251058

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000770

AC:

1126

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

497

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0201

AC:

673

AN:

33474

American (AMR)

AF:

0.00208

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00241

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000156

AC:

174

AN:

1111988

Other (OTH)

AF:

0.00174

AC:

105

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00558

AC:

849

AN:

152208

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

392

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0186

AC:

774

AN:

41526

American (AMR)

AF:

0.00268

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

67996

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00150

Hom.:

Bravo

AF:

0.00651

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00185

AC:

224

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.3

PhyloP100

1.2

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.29

Sift

Benign

0.25

Sift4G

Benign

0.24

Polyphen

0.91

Vest4

0.60

MVP

0.95

MPC

0.61

ClinPred

0.029

GERP RS

5.5

Varity_R

0.75

gMVP

0.64

Mutation Taster

=90/10

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over