7-91266629-C-G

Variant names:

• chr7-91266629-C-G
• NM_003505.2:c.1749C>G
• FZD1 p.His583Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003505.2(FZD1):​c.1749C>G​(p.His583Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H583H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FZD1 NM_003505.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 0 publications found

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

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=0.11114484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003505.2. 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
	FZD1	NM_003505.2	MANE Select	c.1749C>G	p.His583Gln	missense	Exon 1 of 1	NP_003496.1	Q9UP38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD1	ENST00000287934.4	TSL:6 MANE Select	c.1749C>G	p.His583Gln	missense	Exon 1 of 1	ENSP00000287934.2	Q9UP38

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.17	N
PhyloP100		0.17
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.16
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Varity_R		0.16
gMVP		0.53
Mutation Taster		=82/18	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

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

Other links and lift over

hg19: chr7-90895944;