Variant 19-55593339-G-A 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.602C>T(p.Ala201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,311,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709

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=0.06511742).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3 linkuse as main transcript	c.602C>T	p.Ala201Val	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 linkuse as main transcript	c.602C>T	p.Ala201Val	missense_variant	3/3		XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 linkuse as main transcript	c.602C>T	p.Ala201Val	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3 linkuse as main transcript	c.584C>T	p.Ala195Val	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.602C>T	p.Ala201Val	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2		Q96SL8
FIZ1	ENST00000590714.1 linkuse as main transcript	c.*21C>T		downstream_gene_variant		1		ENSP00000465131.1		K7EJE2

Frequencies

GnomAD3 genomes

AF:

0.0000398

AC:

AN:

150716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1161094

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

561186

show subpopulations

Gnomad4 AFR exome

AF:

0.000224

Gnomad4 AMR exome

AF:

0.000240

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000411

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000114

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000398

AC:

AN:

150716

Hom.:

Cov.:

AF XY:

0.0000679

AC XY:

AN XY:

73592

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000453

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

Feb 28, 2024

The c.602C>T (p.A201V) alteration is located in exon 3 (coding exon 2) of the FIZ1 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the alanine (A) at amino acid position 201 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.10

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.93

REVEL

Benign

0.030

Sift

Benign

0.16

Sift4G

Benign

0.24

Polyphen

0.027

Vest4

0.091

MutPred

0.36

Loss of disorder (P = 0.0308);

MVP

0.25

ClinPred

0.082

GERP RS

1.3

Varity_R

0.073

gMVP

0.24

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