Genetic Variant WNT16:p.Thr263Ile (chr7-121339035-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_057168.2(WNT16):c.788C>T(p.Thr263Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,613,634 control chromosomes in the GnomAD database, including 175,418 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.54 ( 24765 hom., cov: 32)

Exomes 𝑓: 0.45 ( 150653 hom. )

Consequence

WNT16
NM_057168.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.610913E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT16	NM_057168.2 link	c.788C>T	p.Thr263Ile	missense_variant	Exon 4 of 4	ENST00000222462.3	NP_476509.1	Q9UBV4-1
WNT16	NM_016087.2 link	c.758C>T	p.Thr253Ile	missense_variant	Exon 4 of 4		NP_057171.2	Q9UBV4E9PH60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3 link	c.788C>T	p.Thr263Ile	missense_variant	Exon 4 of 4	1	NM_057168.2	ENSP00000222462.2		Q9UBV4-1
WNT16	ENST00000361301.6 link	c.758C>T	p.Thr253Ile	missense_variant	Exon 4 of 4	1		ENSP00000355065.2		E9PH60

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82017

AN:

151932

Hom.:

24726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.826

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.514

GnomAD3 exomes

AF:

0.443

AC:

111148

AN:

250812

Hom.:

26796

AF XY:

0.437

AC XY:

59299

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.446

AC:

652129

AN:

1461584

Hom.:

150653

Cov.:

AF XY:

0.445

AC XY:

323279

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.846

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.457

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.540

AC:

82110

AN:

152050

Hom.:

24765

Cov.:

AF XY:

0.529

AC XY:

39278

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.826

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.458

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.466

Hom.:

36923

Bravo

AF:

0.555

TwinsUK

AF:

0.422

AC:

1563

ALSPAC

AF:

0.445

AC:

1716

ESP6500AA

AF:

0.823

AC:

3624

ESP6500EA

AF:

0.456

AC:

3922

ExAC

AF:

0.455

AC:

55176

Asia WGS

AF:

0.363

AC:

1262

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.056

T;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

.;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.099

Sift

Benign

0.27

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0030

B;B

Vest4

0.052

MPC

0.17

ClinPred

0.0017

GERP RS

2.7

Varity_R

0.055

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over