Genetic Variant FZD9:p.Pro109Arg (chr7-73434333-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003508.3(FZD9):c.326C>G(p.Pro109Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,340 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: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FZD9
NM_003508.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Publications

0 publications found

Variant links:

Genes affected

FZD9 (HGNC:4047): (frizzled class receptor 9) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD9 gene is located within the Williams syndrome common deletion region of chromosome 7, and heterozygous deletion of the FZD9 gene may contribute to the Williams syndrome phenotype. FZD9 is expressed predominantly in brain, testis, eye, skeletal muscle, and kidney. [provided by RefSeq, Jul 2008]

FZD9 links:

Genome browser will be placed here

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;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.916

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003508.3. 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
	FZD9	NM_003508.3	MANE Select	c.326C>G	p.Pro109Arg	missense	Exon 1 of 1	NP_003499.1	O00144

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD9	ENST00000344575.5	TSL:6 MANE Select	c.326C>G	p.Pro109Arg	missense	Exon 1 of 1	ENSP00000345785.3	O00144

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000499

AC:

AN:

200540

AF XY:

0.00

show subpopulations

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

AF:

6.99e-7

AC:

AN:

1431340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32140

American (AMR)

AF:

0.00

AC:

AN:

42150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25680

East Asian (EAS)

AF:

0.00

AC:

AN:

38456

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104190

Other (OTH)

AF:

0.00

AC:

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000845

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.71

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.6

PhyloP100

7.4

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.9

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.89

MutPred

0.63

Loss of glycosylation at T106 (P = 0.0491)

MVP

0.80

ClinPred

0.97

GERP RS

2.7

Varity_R

0.78

gMVP

0.78

Mutation Taster

=22/78

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over