8-28527193-T-C

Variant names:

• chr8-28527193-T-C
• NM_017412.4:c.433T>C
• FZD3 p.Leu145Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017412.4(FZD3):​c.433T>C​(p.Leu145Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FZD3 NM_017412.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 0 publications found

Genes affected

FZD3 (HGNC:4041): (frizzled class receptor 3) This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. The function of this protein is unknown, although it may play a role in mammalian hair follicle development. Alternative splicing results in multiple transcript variants. This gene is a susceptibility locus for schizophrenia. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.078 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017412.4. 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
	FZD3	NM_017412.4	MANE Select	c.433T>C	p.Leu145Leu	synonymous	Exon 5 of 8	NP_059108.1	Q9NPG1-1
	FZD3	NM_001412905.1		c.502T>C	p.Leu168Leu	synonymous	Exon 6 of 9	NP_001399834.1
	FZD3	NM_001412917.1		c.502T>C	p.Leu168Leu	synonymous	Exon 5 of 8	NP_001399846.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD3	ENST00000240093.8	TSL:1 MANE Select	c.433T>C	p.Leu145Leu	synonymous	Exon 5 of 8	ENSP00000240093.3	Q9NPG1-1
	FZD3	ENST00000927846.1		c.502T>C	p.Leu168Leu	synonymous	Exon 6 of 9	ENSP00000597905.1
	FZD3	ENST00000537916.2	TSL:2	c.433T>C	p.Leu145Leu	synonymous	Exon 4 of 7	ENSP00000437489.1	Q9NPG1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.78
PhyloP100		-0.078

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-28384710;