22-45923008-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_058238.3(WNT7B):c.898G>T(p.Gly300Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G300S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

WNT7B
NM_058238.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Publications

0 publications found

Variant links:

Genes affected

WNT7B (HGNC:12787): (Wnt family member 7B) This gene is a member of the WNT gene family, which 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. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008]

WNT7B Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

WNT7B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.9927 (below the threshold of 3.09). Trascript score misZ: 1.4346 (below the threshold of 3.09). GenCC associations: The gene is linked to multiple congenital anomalies/dysmorphic syndrome, Tourette syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058238.3. 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
	WNT7B	NM_058238.3	MANE Select	c.898G>T	p.Gly300Cys	missense	Exon 4 of 4	NP_478679.1	P56706
	WNT7B	NM_001410806.1		c.910G>T	p.Gly304Cys	missense	Exon 4 of 4	NP_001397735.1	A8K0G1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT7B	ENST00000339464.9	TSL:1 MANE Select	c.898G>T	p.Gly300Cys	missense	Exon 4 of 4	ENSP00000341032.4	P56706
WNT7B	ENST00000409496.7	TSL:2	c.910G>T	p.Gly304Cys	missense	Exon 4 of 4	ENSP00000386546.3	A8K0G1
WNT7B	ENST00000410089.5	TSL:5	c.850G>T	p.Gly284Cys	missense	Exon 4 of 4	ENSP00000386781.1	B8A595

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.94

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.093

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.67

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.3

PhyloP100

2.7

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0090

Polyphen

0.93

Vest4

0.29

MutPred

0.75

Loss of disorder (P = 0.0313)

MVP

0.95

MPC

1.7

ClinPred

0.98

GERP RS

0.31

Varity_R

0.47

gMVP

0.71

Mutation Taster

=83/17

polymorphism

(source)

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