Variant chr19-49807209-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_025129.5(FUZ):c.1199C>T(p.Thr400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,280 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.032 ( 159 hom., cov: 31)

Exomes 𝑓: 0.010 ( 575 hom. )

Consequence

FUZ
NM_025129.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.216

Variant links:

Genes affected

FUZ (HGNC:26219): (fuzzy planar cell polarity protein) This gene encodes a planar cell polarity protein that is involved in ciliogenesis and directional cell movement. Knockout studies in mice exhibit neural tube defects and defective cilia, and mutations in this gene are associated with neural tube defects in humans. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

FUZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001951158).

BP6

Variant 19-49807209-G-A is Benign according to our data. Variant chr19-49807209-G-A is described in ClinVar as [Benign]. Clinvar id is 3059634.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUZ	NM_025129.5 linkuse as main transcript	c.1199C>T	p.Thr400Ile	missense_variant	11/11	ENST00000313777.9	NP_079405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUZ	ENST00000313777.9 linkuse as main transcript	c.1199C>T	p.Thr400Ile	missense_variant	11/11	1	NM_025129.5	ENSP00000313309	P1	Q9BT04-1

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4848

AN:

151722

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.00482

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.0293

AC:

7322

AN:

250130

Hom.:

353

AF XY:

0.0256

AC XY:

3476

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.0663

Gnomad AMR exome

AF:

0.0717

Gnomad ASJ exome

AF:

0.000998

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.00473

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0102

AC:

14949

AN:

1461438

Hom.:

575

Cov.:

AF XY:

0.0100

AC XY:

7289

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0669

Gnomad4 AMR exome

AF:

0.0734

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.00501

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0320

AC:

4866

AN:

151842

Hom.:

159

Cov.:

AF XY:

0.0337

AC XY:

2498

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0658

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.00482

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.0228

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0383

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0645

AC:

284

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.0265

AC:

3214

Asia WGS

AF:

0.0720

AC:

249

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FUZ-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Uncertain

0.73

.;.;D

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.089

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.064

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.15

MPC

0.23

ClinPred

0.013

GERP RS

0.88

Varity_R

0.095

gMVP

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over