Genetic Variant NM_007146.3:c.1038_1046delGCAGCAGCA (chr17-57979243-TTGCTGCTGC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_007146.3(VEZF1):c.1038_1046delGCAGCAGCA(p.Gln347_Gln349del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00139 in 1,597,074 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

VEZF1
NM_007146.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.35

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 -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_007146.3

BP6

Variant 17-57979243-TTGCTGCTGC-T is Benign according to our data. Variant chr17-57979243-TTGCTGCTGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042684.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3 link	c.1038_1046delGCAGCAGCA	p.Gln347_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENST00000581208.2	NP_009077.2	Q14119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VEZF1	ENST00000581208.2 link	c.1038_1046delGCAGCAGCA	p.Gln347_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	1	NM_007146.3	ENSP00000462337.1	Q14119
VEZF1	ENST00000258963.7 link	c.492_500delGCAGCAGCA	p.Gln165_Gln167del	disruptive_inframe_deletion	Exon 4 of 5	1		ENSP00000258963.3	J9JIC7
VEZF1	ENST00000584396.5 link	c.1011_1019delGCAGCAGCA	p.Gln338_Gln340del	disruptive_inframe_deletion	Exon 5 of 6	5		ENSP00000464687.1	J3QSH4

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

172

AN:

150648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000529

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.0000959

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00183

Gnomad OTH

AF:

0.000484

GnomAD4 exome

AF:

0.00142

AC:

2054

AN:

1446314

Hom.:

AF XY:

0.00139

AC XY:

999

AN XY:

719524

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.000382

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.000266

Gnomad4 NFE exome

AF:

0.00160

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00114

AC:

172

AN:

150760

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

73668

show subpopulations

Gnomad4 AFR

AF:

0.000685

Gnomad4 AMR

AF:

0.000528

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.0000959

Gnomad4 NFE

AF:

0.00183

Gnomad4 OTH

AF:

0.000479

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VEZF1-related disorder

Benign:1

Jun 16, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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