dbSNP rs771330574: FIZ1:p.Ala220Thr (chr19-55593283-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.658G>A(p.Ala220Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,265,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Publications

0 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=0.048925966).

BS2

High AC in GnomAd4 at 5 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.658G>A	p.Ala220Thr	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.658G>A	p.Ala220Thr	missense	Exon 3 of 3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000885049.1		c.769G>A	p.Ala257Thr	missense	Exon 4 of 4	ENSP00000555108.1
FIZ1	ENST00000885048.1		c.658G>A	p.Ala220Thr	missense	Exon 3 of 3	ENSP00000555107.1

Frequencies

GnomAD3 genomes

AF:

0.0000336

AC:

AN:

148818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00146

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:

0.0000515

AC:

AN:

58218

AF XY:

0.0000577

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00182

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:

0.0000358

AC:

AN:

1116342

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

543926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21038

American (AMR)

AF:

0.00

AC:

AN:

11370

Ashkenazi Jewish (ASJ)

AF:

0.00218

AC:

AN:

12412

East Asian (EAS)

AF:

0.00

AC:

AN:

19562

South Asian (SAS)

AF:

0.00

AC:

AN:

49698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26128

Middle Eastern (MID)

AF:

0.000326

AC:

AN:

3064

European-Non Finnish (NFE)

AF:

0.00000966

AC:

AN:

931292

Other (OTH)

AF:

0.0000718

AC:

AN:

41778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.0000336

AC:

AN:

148818

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41128

American (AMR)

AF:

0.00

AC:

AN:

14976

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66698

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.00

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000190

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

0.31

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

0.015

Eigen_PC

Benign

0.0061

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.42

PhyloP100

2.9

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.36

REVEL

Benign

0.075

Sift

Benign

0.43

Sift4G

Benign

0.20

Polyphen

0.89

Vest4

0.25

MutPred

0.55

Gain of glycosylation at A220 (P = 0.0694)

MVP

0.41

ClinPred

0.15

GERP RS

3.3

Varity_R

0.053

gMVP

0.075

Mutation Taster

=91/9

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