Genetic Variant NM_003396.3:c.320G>A (chr17-46872759-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003396.3(WNT9B):c.320G>A(p.Gly107Asp) 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. 16/22 in silico tools predict 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. G107V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WNT9B
NM_003396.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

WNT9B (HGNC:12779): (Wnt family member 9B) 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. Study of its expression in the teratocarcinoma cell line NT2 suggests that it may be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid. This gene is clustered with WNT3, another family member, in the chromosome 17q21 region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

WNT9B links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

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ACMG classification

Classification was made for transcript

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=0.3049708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 2 of 4	ENST00000290015.7	NP_003387.1	O14905
WNT9B	NM_001320458.2 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 2 of 5		NP_001307387.1	E7EPC3
WNT9B	XM_011525178.3 link	c.338G>A	p.Gly113Asp	missense_variant	Exon 2 of 4		XP_011523480.1
LRRC37A2	XM_024450773.2 link	c.4810-176297G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT9B	ENST00000290015.7 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 2 of 4	1	NM_003396.3	ENSP00000290015.2	O14905
WNT9B	ENST00000393461.2 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 2 of 5	2		ENSP00000377105.2	E7EPC3
WNT9B	ENST00000575372.5 link	c.338G>A	p.Gly113Asp	missense_variant	Exon 2 of 3	4		ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723136

African (AFR)

AF:

0.00

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25914

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

85410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108782

Other (OTH)

AF:

0.00

AC:

AN:

59960

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.37

.;T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.031

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.47

.;N;.

PhyloP100

2.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.29

.;N;N

REVEL

Benign

0.20

Sift

Benign

0.58

.;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0, 0.0040

.;B;B

Vest4

0.35, 0.37

MutPred

0.45

.;Loss of MoRF binding (P = 0.0707);Loss of MoRF binding (P = 0.0707);

MVP

0.75

MPC

0.34

ClinPred

0.25

GERP RS

2.3

Varity_R

0.084

gMVP

0.41

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

Below is the list of publications found by LitVar for variant 17:46872759 G>A . It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over