chr7-91265454-G-C

Variant summary

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

The NM_003505.2(FZD1):​c.574G>C​(p.Glu192Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 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

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94
Variant links:
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]

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ACMG classification

Classification made for transcript

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 Protein UniProt
FZD1NM_003505.2 linkuse as main transcriptc.574G>C p.Glu192Gln missense_variant 1/1 ENST00000287934.4 NP_003496.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FZD1ENST00000287934.4 linkuse as main transcriptc.574G>C p.Glu192Gln missense_variant 1/1 NM_003505.2 ENSP00000287934 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2022The c.574G>C (p.E192Q) alteration is located in exon 1 (coding exon 1) of the FZD1 gene. This alteration results from a G to C substitution at nucleotide position 574, causing the glutamic acid (E) at amino acid position 192 to be replaced by a glutamine (Q). 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
Uncertain
0.38
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.070
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.62
Sift
Benign
0.10
T
Sift4G
Benign
0.096
T
Polyphen
0.77
P
Vest4
0.64
MVP
0.89
ClinPred
0.95
D
GERP RS
4.7
Varity_R
0.21
gMVP
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1220181607; hg19: chr7-90894769; API