7-121339035-C-T

Variant names:

• chr7-121339035-C-T
• rs2707466
• NM_057168.2:c.788C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 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.

• Frequency:
  • Genomes: 𝑓 0.54 (24765 hom., cov: 32)
  • Exomes 𝑓: 0.45 (150653 hom.)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 79 publications found

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]

ENSG00000308687 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.788C>T	p.Thr263Ile	missense	Exon 4 of 4	NP_476509.1	Q9UBV4-1
	WNT16	NM_016087.2		c.758C>T	p.Thr253Ile	missense	Exon 4 of 4	NP_057171.2	Q9UBV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT16	ENST00000222462.3	TSL:1 MANE Select	c.788C>T	p.Thr263Ile	missense	Exon 4 of 4	ENSP00000222462.2	Q9UBV4-1
	WNT16	ENST00000361301.6	TSL:1	c.758C>T	p.Thr253Ile	missense	Exon 4 of 4	ENSP00000355065.2	E9PH60
	ENSG00000308687	ENST00000835700.1		n.189-67G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82017 AN: 151932 Hom.: 24726 Cov.: 32

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

GnomAD2 exomes AF: 0.443 AC: 111148 AN: 250812 AF XY: 0.437

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 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.: 57 AF XY: 0.445 AC XY: 323279 AN XY: 727102

African (AFR) AF: 0.846 AC: 28319 AN: 33474

American (AMR) AF: 0.403 AC: 17999 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11936 AN: 26132

East Asian (EAS) AF: 0.150 AC: 5965 AN: 39698

South Asian (SAS) AF: 0.423 AC: 36485 AN: 86256

European-Finnish (FIN) AF: 0.416 AC: 22224 AN: 53402

Middle Eastern (MID) AF: 0.477 AC: 2753 AN: 5768

European-Non Finnish (NFE) AF: 0.449 AC: 499132 AN: 1111778

Other (OTH) AF: 0.452 AC: 27316 AN: 60394

GnomAD4 genome AF: 0.540 AC: 82110 AN: 152050 Hom.: 24765 Cov.: 32 AF XY: 0.529 AC XY: 39278 AN XY: 74306

African (AFR) AF: 0.826 AC: 34300 AN: 41516

American (AMR) AF: 0.424 AC: 6472 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3466

East Asian (EAS) AF: 0.167 AC: 863 AN: 5168

South Asian (SAS) AF: 0.417 AC: 2005 AN: 4810

European-Finnish (FIN) AF: 0.398 AC: 4197 AN: 10546

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31104 AN: 67952

Other (OTH) AF: 0.518 AC: 1094 AN: 2112

Alfa AF: 0.480 Hom.: 78981

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.056	T
MetaRNN	Benign	6.6e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.099
Sift	Benign	0.27	T
Sift4G	Benign	0.19	T
Polyphen		0.0030	B
Vest4		0.052
MPC		0.17
ClinPred		0.0017	T
GERP RS		2.7
Varity_R		0.055
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

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: rs2707466; hg19: chr7-120979089; COSMIC: COSV55975194;