Variant 17-57979245-GC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_007146.3(VEZF1):c.1044del(p.Gln348HisfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,461,200 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0075 ( 13 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 66 hom. )

Consequence

VEZF1
NM_007146.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.333 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 17-57979245-GC-G is Benign according to our data. Variant chr17-57979245-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056872.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00749 (1058/141186) while in subpopulation SAS AF= 0.0288 (134/4650). AF 95% confidence interval is 0.0248. There are 13 homozygotes in gnomad4. There are 556 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1058 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEZF1	NM_007146.3 linkuse as main transcript	c.1044del	p.Gln348HisfsTer9	frameshift_variant	5/6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
VEZF1	ENST00000581208.2 linkuse as main transcript	c.1044del	p.Gln348HisfsTer9	frameshift_variant	5/6	1	NM_007146.3	ENSP00000462337	P2
VEZF1	ENST00000258963.7 linkuse as main transcript	c.500del	p.Gln167HisfsTer9	frameshift_variant	4/5	1		ENSP00000258963
VEZF1	ENST00000584396.5 linkuse as main transcript	c.1017del	p.Gln339HisfsTer9	frameshift_variant	5/6	5		ENSP00000464687	A2

Frequencies

GnomAD3 genomes

AF:

0.00742

AC:

1047

AN:

141084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00488

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0000981

Gnomad MID

AF:

0.0130

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00501

GnomAD3 exomes

AF:

0.000369

AC:

AN:

219524

Hom.:

AF XY:

0.000387

AC XY:

AN XY:

118950

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.0000629

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000594

Gnomad SAS exome

AF:

0.000872

Gnomad FIN exome

AF:

0.000411

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00383

AC:

5059

AN:

1320014

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

2932

AN XY:

658108

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00218

Gnomad4 ASJ exome

AF:

0.000206

Gnomad4 EAS exome

AF:

0.000135

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.000289

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.00554

GnomAD4 genome

AF:

0.00749

AC:

1058

AN:

141186

Hom.:

Cov.:

AF XY:

0.00804

AC XY:

556

AN XY:

69176

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00488

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.0000981

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VEZF1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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