chr7-121329754-A-C

Variant names:

• chr7-121329754-A-C
• rs773585692
• NM_057168.2:c.283A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_057168.2(WNT16):​c.283A>C​(p.Thr95Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.003980428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT16	NM_057168.2	c.283A>C	p.Thr95Pro	missense_variant	Exon 2 of 4	ENST00000222462.3	NP_476509.1
WNT16	NM_016087.2	c.253A>C	p.Thr85Pro	missense_variant	Exon 2 of 4		NP_057171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3	c.283A>C	p.Thr95Pro	missense_variant	Exon 2 of 4	1	NM_057168.2	ENSP00000222462.2
WNT16	ENST00000361301.6	c.253A>C	p.Thr85Pro	missense_variant	Exon 2 of 4	1		ENSP00000355065.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.000706 AC: 166 AN: 235100 Hom.: 0 AF XY: 0.000613 AC XY: 79 AN XY: 128978

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00829

Gnomad NFE exome AF: 0.000417

Gnomad OTH exome AF: 0.000849

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000689 AC: 10 AN: 1452184 Hom.: 0 Cov.: 34 AF XY: 0.00000692 AC XY: 5 AN XY: 722424

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000647

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000499

GnomAD4 genome Cov.: 33

ExAC AF: 0.00128 AC: 155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.52
DEOGEN2	Benign	0.37	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.22	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.20	.;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.17
Sift	Benign	0.26	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.060
MutPred		0.56		.;Loss of MoRF binding (P = 0.1159);
MVP		0.42
MPC		0.20
ClinPred		0.021	T
GERP RS		1.6
Varity_R		0.15
gMVP		0.62

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

Other links and lift over

dbSNP: rs773585692; hg19: chr7-120969808;