7-91265406-G-A

Variant summary

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

The NM_003505.2(FZD1):c.526G>A(p.Val176Met) 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: FZD1 NM_003505.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

Genes affected

FZD1 (HGNC:4038): (frizzled class receptor 1) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD1 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, 7 transmembrane domains, and a C-terminal PDZ domain-binding motif. The FZD1 transcript is expressed in various tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FZD1	NM_003505.2	c.526G>A	p.Val176Met	missense_variant	1/1	ENST00000287934.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FZD1	ENST00000287934.4	c.526G>A	p.Val176Met	missense_variant	1/1		NM_003505.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.526G>A (p.V176M) alteration is located in exon 1 (coding exon 1) of the FZD1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the valine (V) at amino acid position 176 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
Cadd	Pathogenic	32
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.49
Sift	Benign	0.41	T
Sift4G	Benign	0.37	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.62		Loss of catalytic residue at V176 (P = 0.2157);
MVP		0.83
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-90894721;