19-55592548-C-T

Variant names:

• chr19-55592548-C-T
• NM_032836.3:c.1393G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032836.3(FIZ1):​c.1393G>A​(p.Gly465Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIZ1 NM_032836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062186062).

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.1393G>A	p.Gly465Ser	missense	Exon 3 of 3	NP_116225.2	Q96SL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIZ1	ENST00000221665.5	TSL:1 MANE Select	c.1393G>A	p.Gly465Ser	missense	Exon 3 of 3	ENSP00000221665.2	Q96SL8
	FIZ1	ENST00000885049.1		c.1504G>A	p.Gly502Ser	missense	Exon 4 of 4	ENSP00000555108.1
	FIZ1	ENST00000885048.1		c.1393G>A	p.Gly465Ser	missense	Exon 3 of 3	ENSP00000555107.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.056	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.71	N
PhyloP100		1.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.049
Sift	Benign	0.89	T
Sift4G	Benign	0.78	T
Polyphen		0.012	B
Vest4		0.11
MutPred		0.71		Loss of catalytic residue at G465 (P = 0.0688)
MVP		0.099
ClinPred		0.12	T
GERP RS		2.5
Varity_R		0.13
gMVP		0.44
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr19-56103914;