Variant 19-55593136-C-T 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.805G>A(p.Ala269Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 1,204,214 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.128

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=0.004875958).

BS2

High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	3/3		XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3 linkuse as main transcript	c.787G>A	p.Ala263Thr	missense_variant	2/2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIZ1	ENST00000221665.5 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2		Q96SL8

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

147876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000874

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00234

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00101

AC:

AN:

3944

Hom.:

AF XY:

0.000402

AC XY:

AN XY:

2490

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1056230

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

508820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00107

Gnomad4 SAS exome

AF:

0.000679

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000444

Gnomad4 OTH exome

AF:

0.0000763

GnomAD4 genome

AF:

0.000209

AC:

AN:

147984

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

72120

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000873

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00234

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000351

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.805G>A (p.A269T) alteration is located in exon 3 (coding exon 2) of the FIZ1 gene. This alteration results from a G to A substitution at nucleotide position 805, causing the alanine (A) at amino acid position 269 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

DANN

Benign

0.83

DEOGEN2

Benign

0.018

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.42

M_CAP

Benign

0.038

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.33

REVEL

Benign

0.041

Sift

Benign

0.59

Sift4G

Benign

0.68

Polyphen

0.033

Vest4

0.045

MutPred

0.31

Gain of phosphorylation at A269 (P = 0.0035);

MVP

0.17

ClinPred

0.025

GERP RS

-2.5

Varity_R

0.027

gMVP

0.13

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