NM_003506.4:c.97A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003506.4(FZD6):c.97A>G(p.Met33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,606,408 control chromosomes in the GnomAD database, including 50,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4285 hom., cov: 31)

Exomes 𝑓: 0.25 ( 45822 hom. )

Consequence

FZD6
NM_003506.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0290

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047037303).

BP6

Variant 8-103300204-A-G is Benign according to our data. Variant chr8-103300204-A-G is described in ClinVar as [Benign]. Clinvar id is 1285287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD6	NM_003506.4 link	c.97A>G	p.Met33Val	missense_variant	Exon 2 of 7	ENST00000358755.5	NP_003497.2	O60353-1A0A024R9E9B4E236

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD6	ENST00000358755.5 link	c.97A>G	p.Met33Val	missense_variant	Exon 2 of 7	1	NM_003506.4	ENSP00000351605.4		O60353-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35134

AN:

151962

Hom.:

4289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.248

GnomAD3 exomes

AF:

0.217

AC:

54480

AN:

251446

Hom.:

6794

AF XY:

0.223

AC XY:

30316

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.00739

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.245

AC:

356430

AN:

1454328

Hom.:

45822

Cov.:

AF XY:

0.245

AC XY:

177311

AN XY:

724002

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.00512

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.231

AC:

35156

AN:

152080

Hom.:

4285

Cov.:

AF XY:

0.227

AC XY:

16886

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.258

Hom.:

10751

Bravo

AF:

0.227

TwinsUK

AF:

0.259

AC:

960

ALSPAC

AF:

0.243

AC:

938

ESP6500AA

AF:

0.211

AC:

930

ESP6500EA

AF:

0.265

AC:

2279

ExAC

AF:

0.224

AC:

27155

Asia WGS

AF:

0.101

AC:

353

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.277

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nonsyndromic congenital nail disorder 1

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.7

DANN

Benign

0.88

DEOGEN2

Benign

0.20

T;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.61

.;T;D

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.54

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.039

MPC

0.26

ClinPred

0.00048

GERP RS

-0.68

Varity_R

0.080

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over