chr19-55592548-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIZ1	NM_032836.3	c.1393G>A	p.Gly465Ser	missense_variant	Exon 3 of 3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5	c.1393G>A	p.Gly465Ser	missense_variant	Exon 3 of 3		XP_005259409.1
FIZ1	XM_047439564.1	c.1393G>A	p.Gly465Ser	missense_variant	Exon 2 of 2		XP_047295520.1
FIZ1	XM_011527426.3	c.1375G>A	p.Gly459Ser	missense_variant	Exon 2 of 2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIZ1	ENST00000221665.5	c.1393G>A	p.Gly465Ser	missense_variant	Exon 3 of 3	1	NM_032836.3	ENSP00000221665.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1393G>A (p.G465S) 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 1393, causing the glycine (G) at amino acid position 465 to be replaced by a serine (S). 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	0.21
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-56103914;