Variant 1-227921987-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BS2

The NM_003395.4(WNT9A):c.629G>T(p.Gly210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

WNT9A
NM_003395.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

WNT9A (HGNC:12778): (Wnt family member 9A) The WNT gene family consists of structurally related genes that 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 is expressed in gastric cancer cell lines. The protein encoded by this gene shows 75% amino acid identity to chicken Wnt14, which has been shown to play a central role in initiating synovial joint formation in the chick limb. This gene is clustered with another family member, WNT3A, in the chromosome 1q42 region. [provided by RefSeq, Jul 2008]

WNT9A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9A	NM_003395.4 linkuse as main transcript	c.629G>T	p.Gly210Val	missense_variant	4/4	ENST00000272164.6	NP_003386.1
WNT9A	XM_011544271.3 linkuse as main transcript	c.419G>T	p.Gly140Val	missense_variant	4/4		XP_011542573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT9A	ENST00000272164.6 linkuse as main transcript	c.629G>T	p.Gly210Val	missense_variant	4/4	1	NM_003395.4	ENSP00000272164	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1455108

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.629G>T (p.G210V) alteration is located in exon 4 (coding exon 4) of the WNT9A gene. This alteration results from a G to T substitution at nucleotide position 629, causing the glycine (G) at amino acid position 210 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.54

Sift

Uncertain

0.0040

Sift4G

Benign

0.47

Polyphen

0.99

Vest4

0.64

MutPred

0.45

Gain of ubiquitination at K208 (P = 0.0682);

MVP

0.97

MPC

1.3

ClinPred

0.99

GERP RS

4.4

Varity_R

0.88

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over