Genetic Variant NM_003396.3:c.214C>T (chr17-46872653-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003396.3(WNT9B):c.214C>T(p.Pro72Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WNT9B
NM_003396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.73

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003396.3. 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
	WNT9B	NM_003396.3	MANE Select	c.214C>T	p.Pro72Ser	missense	Exon 2 of 4	NP_003387.1	O14905
	WNT9B	NM_001320458.2		c.214C>T	p.Pro72Ser	missense	Exon 2 of 5	NP_001307387.1	E7EPC3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT9B	ENST00000290015.7	TSL:1 MANE Select	c.214C>T	p.Pro72Ser	missense	Exon 2 of 4	ENSP00000290015.2	O14905
WNT9B	ENST00000393461.2	TSL:2	c.214C>T	p.Pro72Ser	missense	Exon 2 of 5	ENSP00000377105.2	E7EPC3
WNT9B	ENST00000575372.5	TSL:4	c.232C>T	p.Pro78Ser	missense	Exon 2 of 3	ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249376

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726960

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111952

Other (OTH)

AF:

0.00

AC:

AN:

60342

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.7

PhyloP100

7.7

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.68

Sift

Uncertain

0.010

Sift4G

Uncertain

0.029

Polyphen

0.86

Vest4

0.77

MutPred

0.65

Gain of phosphorylation at P72 (P = 0.0084)

MVP

0.89

MPC

0.93

ClinPred

0.99

GERP RS

3.5

Varity_R

0.50

gMVP

0.75

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over