17-57974895-C-A

Position:

• chr17-57974895-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000581208.2(VEZF1):​c.1144G>T​(p.Ala382Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: VEZF1 ENST00000581208.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

Genes affected

VEZF1 (HGNC:12949): (vascular endothelial zinc finger 1) Transcriptional regulatory proteins containing tandemly repeated zinc finger domains are thought to be involved in both normal and abnormal cellular proliferation and differentiation. ZNF161 is a C2H2-type zinc finger protein (Koyano-Nakagawa et al., 1994 [PubMed 8035792]). See MIM 603971 for general information on zinc finger proteins.[supplied by OMIM, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), VEZF1. . Gene score misZ 2.9212 (greater than the threshold 3.09). Trascript score misZ 4.5405 (greater than threshold 3.09). GenCC has associacion of gene with cardiomyopathy, dilated, 100, autism spectrum disorder.
• BP4: Computational evidence support a benign effect (MetaRNN=0.10299933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1144G>T	p.Ala382Ser	missense_variant	6/6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEZF1	ENST00000581208.2	c.1144G>T	p.Ala382Ser	missense_variant	6/6	1	NM_007146.3	ENSP00000462337.1
VEZF1	ENST00000258963.7	c.598G>T	p.Ala200Ser	missense_variant	5/5	1		ENSP00000258963.3
VEZF1	ENST00000584396.5	c.1117G>T	p.Ala373Ser	missense_variant	6/6	5		ENSP00000464687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 01, 2024

The c.1144G>T (p.A382S) alteration is located in exon 6 (coding exon 6) of the VEZF1 gene. This alteration results from a G to T substitution at nucleotide position 1144, causing the alanine (A) at amino acid position 382 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	0.11
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0092	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.47	T;T
Polyphen		0.0040	.;B
Vest4		0.091
MutPred		0.47		.;Gain of loop (P = 0);
MVP		0.068
MPC		0.81
ClinPred		0.43	T
GERP RS		6.1
Varity_R		0.045
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr17-56052256;