Variant 19-49808587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000313777.9(FUZ):c.945C>T(p.Pro315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,611,384 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 22 hom. )

Consequence

FUZ
ENST00000313777.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0690

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 19-49808587-G-A is Benign according to our data. Variant chr19-49808587-G-A is described in ClinVar as [Benign]. Clinvar id is 708252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.069 with no splicing effect.

BS2

High AC in GnomAd4 at 496 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUZ	NM_025129.5 linkuse as main transcript	c.945C>T	p.Pro315=	synonymous_variant	9/11	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.945C>T	p.Pro315=	synonymous_variant	9/11	1	NM_025129.5	ENSP00000313309	P1	Q9BT04-1

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

496

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00570

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00350

AC:

854

AN:

244256

Hom.:

AF XY:

0.00361

AC XY:

478

AN XY:

132562

show subpopulations

Gnomad AFR exome

AF:

0.000832

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000768

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00644

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00483

AC:

7052

AN:

1459104

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

3437

AN XY:

725586

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00167

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000735

Gnomad4 FIN exome

AF:

0.00173

Gnomad4 NFE exome

AF:

0.00591

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.00326

AC:

496

AN:

152280

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00570

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00444

Hom.:

Bravo

AF:

0.00343

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	FUZ: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.9

DANN

Benign

0.89

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