rs151339002

Variant summary

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

The NM_003506.4(FZD6):​c.1750G>A​(p.Glu584Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 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: 32)

Consequence

FZD6
NM_003506.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.13
Variant links:
Genes affected
FZD6 (HGNC:4044): (frizzled class receptor 6) This gene represents a member of the 'frizzled' gene family, which encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The protein encoded by this family member contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and seven transmembrane domains, but unlike other family members, this protein does not contain a C-terminal PDZ domain-binding motif. This protein functions as a negative regulator of the canonical Wnt/beta-catenin signaling cascade, thereby inhibiting the processes that trigger oncogenic transformation, cell proliferation, and inhibition of apoptosis. Alternative splicing results in multiple transcript variants, some of which do not encode a protein with a predicted signal peptide.[provided by RefSeq, Aug 2011]

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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
FZD6NM_003506.4 linkuse as main transcriptc.1750G>A p.Glu584Lys missense_variant 6/7 ENST00000358755.5 NP_003497.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FZD6ENST00000358755.5 linkuse as main transcriptc.1750G>A p.Glu584Lys missense_variant 6/71 NM_003506.4 ENSP00000351605 P1O60353-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
0.0023
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T;.
Eigen
Benign
0.096
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Benign
0.025
D
MetaRNN
Uncertain
0.49
T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.7
L;L;.
MutationTaster
Benign
0.98
D;D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.71
N;N;N
REVEL
Benign
0.25
Sift
Benign
0.037
D;D;D
Sift4G
Benign
0.14
T;T;T
Polyphen
0.058
B;B;.
Vest4
0.58
MutPred
0.31
Gain of ubiquitination at E584 (P = 0.0094);Gain of ubiquitination at E584 (P = 0.0094);.;
MVP
0.85
MPC
0.31
ClinPred
0.72
D
GERP RS
5.5
Varity_R
0.23
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs151339002; hg19: chr8-104342091; API