NM_003506.4:c.158T>C

Variant names:

• chr8-103300265-T-C
• NM_003506.4:c.158T>C

Variant summary

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

The NM_003506.4(FZD6):​c.158T>C​(p.Ile53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FZD6 NM_003506.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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]

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=0.123030424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD6	NM_003506.4	c.158T>C	p.Ile53Thr	missense_variant	Exon 2 of 7	ENST00000358755.5	NP_003497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD6	ENST00000358755.5	c.158T>C	p.Ile53Thr	missense_variant	Exon 2 of 7	1	NM_003506.4	ENSP00000351605.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458896 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.70
DEOGEN2	Benign	0.18	T;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.40	N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.3	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.039
MutPred		0.52		Gain of disorder (P = 0.0252);Gain of disorder (P = 0.0252);.;
MVP		0.75
MPC		0.32
ClinPred		0.080	T
GERP RS		0.69
Varity_R		0.054
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-104312493;