Genetic Variant FIZ1:p.Ala269Ser (chr19-55593136-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032836.3(FIZ1):c.805G>T(p.Ala269Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A269T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0422844).

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>T	p.Ala269Ser	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>T	p.Ala269Ser	missense	Exon 3 of 3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000885049.1		c.916G>T	p.Ala306Ser	missense	Exon 4 of 4	ENSP00000555108.1
FIZ1	ENST00000885048.1		c.805G>T	p.Ala269Ser	missense	Exon 3 of 3	ENSP00000555107.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147876

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

3944

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1056232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508822

African (AFR)

AF:

0.00

AC:

AN:

19244

American (AMR)

AF:

0.00

AC:

AN:

6042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10920

East Asian (EAS)

AF:

0.00

AC:

AN:

15954

South Asian (SAS)

AF:

0.00

AC:

AN:

39794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

899918

Other (OTH)

AF:

0.00

AC:

AN:

39338

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

147876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72002

African (AFR)

AF:

0.00

AC:

AN:

41014

American (AMR)

AF:

0.00

AC:

AN:

14870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66412

Other (OTH)

AF:

0.00

AC:

AN:

2034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.5

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.34

M_CAP

Benign

0.024

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-0.13

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.28

REVEL

Benign

0.017

Sift

Benign

0.73

Sift4G

Benign

0.83

Polyphen

0.0

Vest4

0.046

MutPred

0.29

Gain of glycosylation at A269 (P = 0)

MVP

0.19

ClinPred

0.082

GERP RS

-2.5

Varity_R

0.041

gMVP

0.096

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over