Variant 17-57974841-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000581208.2(VEZF1):c.1198C>T(p.Pro400Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VEZF1
ENST00000581208.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

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]

VEZF1 links:

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ACMG classification

Classification made for transcript

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=0.26185358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEZF1	NM_007146.3 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	6/6	ENST00000581208.2	NP_009077.2	Q14119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VEZF1	ENST00000581208.2 linkuse as main transcript	c.1198C>T	p.Pro400Ser	missense_variant	6/6	1	NM_007146.3	ENSP00000462337.1	Q14119
VEZF1	ENST00000258963.7 linkuse as main transcript	c.652C>T	p.Pro218Ser	missense_variant	5/5	1		ENSP00000258963.3	J9JIC7
VEZF1	ENST00000584396.5 linkuse as main transcript	c.1171C>T	p.Pro391Ser	missense_variant	6/6	5		ENSP00000464687.1	J3QSH4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 20, 2023

The c.1198C>T (p.P400S) alteration is located in exon 6 (coding exon 6) of the VEZF1 gene. This alteration results from a C to T substitution at nucleotide position 1198, causing the proline (P) at amino acid position 400 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

0.24

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.026

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

Sift4G

Uncertain

0.032

D;D

Polyphen

0.26

.;B

Vest4

0.54

MutPred

0.20

.;Gain of glycosylation at P400 (P = 0.0323);

MVP

0.15

MPC

0.85

ClinPred

0.53

GERP RS

6.1

Varity_R

0.066

gMVP

0.40

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