Variant chr19-55593057-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032836.3(FIZ1):c.884T>G(p.Leu295Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 1,376,794 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 68 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.610

Variant links:

Genes affected

FIZ1 (HGNC:25917): (FLT3 interacting zinc finger 1) This gene encodes zinc finger protein, which interacts with a receptor tyrosine kinase involved in the regulation of hematopoietic and lymphoid cells. This gene product also interacts with a transcription factor that regulates the expression of rod-specific genes in retina. [provided by RefSeq, Jul 2008]

FIZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063140094).

BS2

High AC in GnomAd4 at 1060 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3 link	c.884T>G	p.Leu295Arg	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 link	c.884T>G	p.Leu295Arg	missense_variant	3/3		XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 link	c.884T>G	p.Leu295Arg	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3 link	c.866T>G	p.Leu289Arg	missense_variant	2/2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIZ1	ENST00000221665.5 link	c.884T>G	p.Leu295Arg	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2		Q96SL8

Frequencies

GnomAD3 genomes

AF:

0.00704

AC:

1059

AN:

150362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00134

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00689

Gnomad ASJ

AF:

0.00812

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00722

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00824

GnomAD3 exomes

AF:

0.00598

AC:

AN:

16052

Hom.:

AF XY:

0.00642

AC XY:

AN XY:

9966

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00766

Gnomad OTH exome

AF:

0.00787

GnomAD4 exome

AF:

0.00923

AC:

11319

AN:

1226322

Hom.:

Cov.:

AF XY:

0.00910

AC XY:

5468

AN XY:

600666

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00426

Gnomad4 ASJ exome

AF:

0.00683

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00888

GnomAD4 genome

AF:

0.00704

AC:

1060

AN:

150472

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

493

AN XY:

73534

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00688

Gnomad4 ASJ

AF:

0.00812

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00722

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00815

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00669

ExAC

AF:

0.00186

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Aug 10, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.042

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.4

REVEL

Benign

0.088

Sift

Benign

0.089

Sift4G

Benign

0.50

Polyphen

0.98

Vest4

0.24

MVP

0.31

ClinPred

0.024

GERP RS

2.0

Varity_R

0.18

gMVP

0.40

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