Variant 19-55593274-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032836.3(FIZ1):c.667A>C(p.Thr223Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.597

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2119902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3 link	c.667A>C	p.Thr223Pro	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 link	c.667A>C	p.Thr223Pro	missense_variant	3/3		XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 link	c.667A>C	p.Thr223Pro	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3 link	c.649A>C	p.Thr217Pro	missense_variant	2/2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIZ1	ENST00000221665.5 link	c.667A>C	p.Thr223Pro	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2		Q96SL8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148492

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000901

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00339

AC:

3785

AN:

1115668

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

1767

AN XY:

545160

show subpopulations

Gnomad4 AFR exome

AF:

0.00306

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00208

Gnomad4 EAS exome

AF:

0.000979

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00373

Gnomad4 OTH exome

AF:

0.00327

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

AN:

148602

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

AN XY:

72480

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000201

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000433

Gnomad4 NFE

AF:

0.0000901

Gnomad4 OTH

AF:

0.00

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

May 05, 2023

The c.667A>C (p.T223P) alteration is located in exon 3 (coding exon 2) of the FIZ1 gene. This alteration results from a A to C substitution at nucleotide position 667, causing the threonine (T) at amino acid position 223 to be replaced by a proline (P). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.18

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

0.38

Vest4

0.22

MutPred

0.54

Gain of disorder (P = 0.0217);

MVP

0.38

ClinPred

0.33

GERP RS

2.4

Varity_R

0.55

gMVP

0.47

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