NM_003468.4:c.1390G>A

Variant names:

• chr2-207767350-C-T
• rs2105851283
• NM_003468.4:c.1390G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003468.4(FZD5):​c.1390G>A​(p.Val464Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FZD5 NM_003468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1390G>A	p.Val464Met	missense	Exon 2 of 2	NP_003459.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD5	ENST00000295417.4	TSL:1 MANE Select	c.1390G>A	p.Val464Met	missense	Exon 2 of 2	ENSP00000354607.3	Q13467
	FZD5	ENST00000908573.1		c.1390G>A	p.Val464Met	missense	Exon 2 of 2	ENSP00000578632.1
	FZD5	ENST00000937374.1		c.1390G>A	p.Val464Met	missense	Exon 2 of 2	ENSP00000607433.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.027	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.74		Loss of catalytic residue at V464 (P = 0.0696)
MVP		0.78
ClinPred		0.99	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.59
gMVP		0.81
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs2105851283; hg19: chr2-208632074;