dbSNP rs1351482936: FZD5:p.Arg566Gly (chr2-207767044-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003468.4(FZD5):c.1696A>G(p.Arg566Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FZD5
NM_003468.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Publications

0 publications found

Variant links:

Genes affected

FZD5 (HGNC:4043): (frizzled class receptor 5) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD5 protein is believed to be the receptor for the Wnt5A ligand. [provided by RefSeq, Jul 2008]

FZD5 Gene-Disease associations (from GenCC):

microphthalmia/coloboma 11
Inheritance: AD Classification: STRONG Submitted by: G2P

FZD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23609939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003468.4. 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
	FZD5	NM_003468.4	MANE Select	c.1696A>G	p.Arg566Gly	missense	Exon 2 of 2	NP_003459.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FZD5	ENST00000295417.4	TSL:1 MANE Select	c.1696A>G	p.Arg566Gly	missense	Exon 2 of 2	ENSP00000354607.3	Q13467
FZD5	ENST00000908573.1		c.1696A>G	p.Arg566Gly	missense	Exon 2 of 2	ENSP00000578632.1
FZD5	ENST00000937374.1		c.1696A>G	p.Arg566Gly	missense	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1364306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674164

African (AFR)

AF:

0.00

AC:

AN:

27538

American (AMR)

AF:

0.00

AC:

AN:

28210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20300

East Asian (EAS)

AF:

0.00

AC:

AN:

35688

South Asian (SAS)

AF:

0.00

AC:

AN:

70948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5022

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075014

Other (OTH)

AF:

0.00

AC:

AN:

56148

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

0.0020

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.025

Sift4G

Benign

0.17

Polyphen

0.70

Vest4

0.062

MutPred

0.26

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.75

ClinPred

0.63

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.32

gMVP

0.77

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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