Variant 19-55593393-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032836.3(FIZ1):c.548G>A(p.Ser183Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000327 in 1,405,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

FIZ1
NM_032836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.387

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08577523).

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3 linkuse as main transcript	c.548G>A	p.Ser183Asn	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 linkuse as main transcript	c.548G>A	p.Ser183Asn	missense_variant	3/3		XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 linkuse as main transcript	c.548G>A	p.Ser183Asn	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3 linkuse as main transcript	c.530G>A	p.Ser177Asn	missense_variant	2/2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FIZ1	ENST00000221665.5 linkuse as main transcript	c.548G>A	p.Ser183Asn	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000590714.1 linkuse as main transcript	c.548G>A	p.Ser183Asn	missense_variant	2/2	1		ENSP00000465131.1	K7EJE2
FIZ1	ENST00000587678.1 linkuse as main transcript	c.*237G>A		downstream_gene_variant		2		ENSP00000468342.1	K7ERP0
FIZ1	ENST00000592585.1 linkuse as main transcript	c.*106G>A		downstream_gene_variant		5		ENSP00000468529.1	K7ES33

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

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

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1253170

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

611804

show subpopulations

Gnomad4 AFR exome

AF:

0.000711

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000184

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000676

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000227

ExAC

AF:

0.000150

AC:

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

Apr 27, 2023

The c.548G>A (p.S183N) alteration is located in exon 3 (coding exon 2) of the FIZ1 gene. This alteration results from a G to A substitution at nucleotide position 548, causing the serine (S) at amino acid position 183 to be replaced by an asparagine (N). 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

0.30

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.10

N;.

REVEL

Benign

0.018

Sift

Benign

0.17

T;.

Sift4G

Benign

0.46

T;.

Polyphen

0.037

B;.

Vest4

0.097

MutPred

0.23

Loss of glycosylation at S183 (P = 0.0309);Loss of glycosylation at S183 (P = 0.0309);

MVP

0.18

ClinPred

0.046

GERP RS

2.3

Varity_R

0.077

gMVP

0.38

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