Genetic Variant FIZ1:p.Ala372Thr (chr19-55592827-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032836.3(FIZ1):c.1114G>A(p.Ala372Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000493 in 1,418,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12246999).

BS2

High AC in GnomAdExome4 at 7 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.1114G>A	p.Ala372Thr	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.1114G>A	p.Ala372Thr	missense	Exon 3 of 3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000885049.1		c.1225G>A	p.Ala409Thr	missense	Exon 4 of 4	ENSP00000555108.1
FIZ1	ENST00000885048.1		c.1114G>A	p.Ala372Thr	missense	Exon 3 of 3	ENSP00000555107.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

179320

AF XY:

0.0000100

show subpopulations

Gnomad AFR exome

AF:

0.000102

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000493

AC:

AN:

1418538

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

703890

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32634

American (AMR)

AF:

0.00

AC:

AN:

40218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.00

AC:

AN:

38320

South Asian (SAS)

AF:

0.00

AC:

AN:

83588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4924

European-Non Finnish (NFE)

AF:

0.00000548

AC:

AN:

1095758

Other (OTH)

AF:

0.00

AC:

AN:

58710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000193

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

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.57

M_CAP

Benign

0.062

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

PhyloP100

0.95

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.53

REVEL

Benign

0.080

Sift

Benign

1.0

Sift4G

Benign

0.53

Polyphen

0.99

Vest4

0.20

MutPred

0.28

Gain of glycosylation at A372 (P = 0.0296)

MVP

0.45

ClinPred

0.16

GERP RS

3.4

Varity_R

0.057

gMVP

0.24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over