Genetic Variant FIZ1:p.Ala269Thr (chr19-55593136-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/22 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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004875958).

BS2

High AC in GnomAd4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032836.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIZ1	NM_032836.3	MANE Select	c.805G>A	p.Ala269Thr	missense	Exon 3 of 3	NP_116225.2	Q96SL8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FIZ1	ENST00000221665.5	TSL:1 MANE Select	c.805G>A	p.Ala269Thr	missense	Exon 3 of 3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000885049.1		c.916G>A	p.Ala306Thr	missense	Exon 4 of 4	ENSP00000555108.1
FIZ1	ENST00000885048.1		c.805G>A	p.Ala269Thr	missense	Exon 3 of 3	ENSP00000555107.1

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

GnomAD2 exomes

AF:

0.00101

AC:

AN:

3944

AF XY:

0.000402

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 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

African (AFR)

AF:

0.00

AC:

AN:

19244

American (AMR)

AF:

0.00215

AC:

AN:

6042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10920

East Asian (EAS)

AF:

0.00107

AC:

AN:

15954

South Asian (SAS)

AF:

0.000679

AC:

AN:

39792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22390

Middle Eastern (MID)

AF:

0.000380

AC:

AN:

2632

European-Non Finnish (NFE)

AF:

0.00000444

AC:

AN:

899918

Other (OTH)

AF:

0.0000763

AC:

AN:

39338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000209

AC:

AN:

147984

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

72120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41132

American (AMR)

AF:

0.000873

AC:

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00234

AC:

AN:

5118

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66402

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000351

ExAC

AF:

0.000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

(source)

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

PhyloP100

-0.13

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over