chr19-55592778-T-G

Position:

• chr19-55592778-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032836.3(FIZ1):​c.1163A>C​(p.Glu388Ala) 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: 33)
• Consequence: FIZ1 NM_032836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.198

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=0.05951646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIZ1	NM_032836.3	c.1163A>C	p.Glu388Ala	missense_variant	3/3	ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5	c.1163A>C	p.Glu388Ala	missense_variant	3/3		XP_005259409.1
FIZ1	XM_047439564.1	c.1163A>C	p.Glu388Ala	missense_variant	2/2		XP_047295520.1
FIZ1	XM_011527426.3	c.1145A>C	p.Glu382Ala	missense_variant	2/2		XP_011525728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIZ1	ENST00000221665.5	c.1163A>C	p.Glu388Ala	missense_variant	3/3	1	NM_032836.3	ENSP00000221665.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1163A>C (p.E388A) 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 1163, causing the glutamic acid (E) at amino acid position 388 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.50
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.031
Sift	Benign	0.38	T
Sift4G	Benign	0.45	T
Polyphen		0.017	B
Vest4		0.16
MutPred		0.43		Gain of glycosylation at T391 (P = 0.1377);
MVP		0.17
ClinPred		0.018	T
GERP RS		0.0014
Varity_R		0.037
gMVP		0.41

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: chr19-56104144;