7-121329754-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_057168.2(WNT16):​c.283A>G​(p.Thr95Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T95S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.57
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047352105).
• BP6: Variant 7-121329754-A-G is Benign according to our data. Variant chr7-121329754-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2620438.Status of the report is criteria_provided_single_submitter, 1 stars.

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.283A>G	p.Thr95Ala	missense	Exon 2 of 4	NP_476509.1	Q9UBV4-1
	WNT16	NM_016087.2		c.253A>G	p.Thr85Ala	missense	Exon 2 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.283A>G	p.Thr95Ala	missense	Exon 2 of 4	ENSP00000222462.2	Q9UBV4-1
	WNT16	ENST00000361301.6	TSL:1	c.253A>G	p.Thr85Ala	missense	Exon 2 of 4	ENSP00000355065.2	E9PH60

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000425 AC: 1 AN: 235100 AF XY: 0.00000775

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000927

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452184 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722424

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 85972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111116

Other (OTH) AF: 0.00 AC: 0 AN: 60154

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.6
DANN	Benign	0.50
DEOGEN2	Benign	0.37	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.040	N
PhyloP100		-2.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.053
Sift	Benign	0.76	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.39		Loss of glycosylation at T95 (P = 0.0801)
MVP		0.53
MPC		0.15
ClinPred		0.025	T
GERP RS		1.6
Varity_R		0.056
gMVP		0.29
Mutation Taster		=91/9	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: rs773585692; hg19: chr7-120969808;