NM_017412.4:c.435A>T

Variant names:

• chr8-28527195-A-T
• rs2241802
• NM_017412.4:c.435A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017412.4(FZD3):​c.435A>T​(p.Leu145Phe) 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. 16/21 in silico tools predict 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: 30)
• Consequence: FZD3 NM_017412.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13817134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD3	NM_017412.4	c.435A>T	p.Leu145Phe	missense_variant	Exon 5 of 8	ENST00000240093.8	NP_059108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD3	ENST00000240093.8	c.435A>T	p.Leu145Phe	missense_variant	Exon 5 of 8	1	NM_017412.4	ENSP00000240093.3
FZD3	ENST00000537916.2	c.435A>T	p.Leu145Phe	missense_variant	Exon 4 of 7	2		ENSP00000437489.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.84	T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.13
Sift	Benign	0.72	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.023	B;B
Vest4		0.26
MutPred		0.32		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.60
MPC		0.74
ClinPred		0.050	T
GERP RS		2.4
Varity_R		0.033
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs2241802; hg19: chr8-28384712;