7-121329323-C-T

Variant names:

• chr7-121329323-C-T
• rs867332829
• NM_057168.2:c.31C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_057168.2(WNT16):​c.31C>T​(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R11G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4238448).

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.31C>T	p.Arg11Cys	missense	Exon 1 of 4	NP_476509.1	Q9UBV4-1
	WNT16	NM_016087.2		c.66-244C>T		intron	N/A	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.31C>T	p.Arg11Cys	missense	Exon 1 of 4	ENSP00000222462.2	Q9UBV4-1
	WNT16	ENST00000361301.6	TSL:1	c.66-244C>T		intron	N/A	ENSP00000355065.2	E9PH60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440816 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 714470

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 40616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 38960

South Asian (SAS) AF: 0.00 AC: 0 AN: 83552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102176

Other (OTH) AF: 0.00 AC: 0 AN: 59654

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.039
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.16	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.019	D
Sift4G	Benign	0.15	T
Polyphen		0.85	P
Vest4		0.43
MutPred		0.66		Gain of catalytic residue at L12 (P = 0.0095)
MVP		0.85
MPC		0.21
ClinPred		0.71	D
GERP RS		4.6
PromoterAI		0.040	Neutral
Varity_R		0.10
gMVP		0.62
Mutation Taster		=89/11	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: rs867332829; hg19: chr7-120969377;