Variant chr8-103325139-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000358755.5(FZD6):c.1033A>C(p.Met345Leu) variant causes a missense change. The variant allele was found at a frequency of 0.462 in 1,613,692 control chromosomes in the GnomAD database, including 175,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 14562 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160796 hom. )

Consequence

FZD6
ENST00000358755.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79

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]

FZD6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.156825E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD6	NM_003506.4 linkuse as main transcript	c.1033A>C	p.Met345Leu	missense_variant	4/7	ENST00000358755.5	NP_003497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD6	ENST00000358755.5 linkuse as main transcript	c.1033A>C	p.Met345Leu	missense_variant	4/7	1	NM_003506.4	ENSP00000351605	P1	O60353-1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65135

AN:

151916

Hom.:

14553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.472

AC:

118587

AN:

251410

Hom.:

29051

AF XY:

0.465

AC XY:

63226

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.627

Gnomad SAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.465

AC:

680381

AN:

1461658

Hom.:

160796

Cov.:

AF XY:

0.464

AC XY:

337391

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.305

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.620

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.429

AC:

65170

AN:

152034

Hom.:

14562

Cov.:

AF XY:

0.429

AC XY:

31906

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.614

Gnomad4 SAS

AF:

0.439

Gnomad4 FIN

AF:

0.443

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.452

Hom.:

38720

Bravo

AF:

0.428

TwinsUK

AF:

0.473

AC:

1753

ALSPAC

AF:

0.475

AC:

1829

ESP6500AA

AF:

0.304

AC:

1341

ESP6500EA

AF:

0.466

AC:

4010

ExAC

AF:

0.462

AC:

56141

Asia WGS

AF:

0.539

AC:

1873

AN:

3478

EpiCase

AF:

0.447

EpiControl

AF:

0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.30

T;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

.;T;T

MetaRNN

Benign

0.000052

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.075

N;N;.

MutationTaster

Benign

0.0095

P;P;P;P

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0080

B;B;.

Vest4

0.10

MutPred

0.22

Loss of methylation at K347 (P = 0.097);Loss of methylation at K347 (P = 0.097);.;

MPC

0.26

ClinPred

0.040

GERP RS

6.2

Varity_R

0.28

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over