Genetic Variant VEZF1:p.Gln347_Gln349dup (chr17-57979243-T-TTGCTGCTGC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_007146.3(VEZF1):c.1038_1046dupGCAGCAGCA(p.Gln347_Gln349dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 150,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. Q349Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0016 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

VEZF1
NM_007146.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.405

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_007146.3

BP6

Variant 17-57979243-T-TTGCTGCTGC is Benign according to our data. Variant chr17-57979243-T-TTGCTGCTGC is described in ClinVar as [Likely_benign]. Clinvar id is 3033431.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3 link	c.1038_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	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_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	1	NM_007146.3	ENSP00000462337.1	Q14119
VEZF1	ENST00000258963.7 link	c.492_500dupGCAGCAGCA	p.Gln165_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	1		ENSP00000258963.3	J9JIC7
VEZF1	ENST00000584396.5 link	c.1011_1019dupGCAGCAGCA	p.Gln338_Gln340dup	disruptive_inframe_insertion	Exon 5 of 6	5		ENSP00000464687.1	J3QSH4

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

171

AN:

150648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000588

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.000727

Gnomad ASJ

AF:

0.00551

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.0000959

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00194

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00159

AC:

2303

AN:

1446168

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1135

AN XY:

719462

show subpopulations

Gnomad4 AFR exome

AF:

0.000972

AC:

AN:

32926

Gnomad4 AMR exome

AF:

0.00120

AC:

AN:

44322

Gnomad4 ASJ exome

AF:

0.00473

AC:

122

AN:

25812

Gnomad4 EAS exome

AF:

0.00107

AC:

AN:

39304

Gnomad4 SAS exome

AF:

0.00101

AC:

AN:

84802

Gnomad4 FIN exome

AF:

0.0000950

AC:

AN:

52620

Gnomad4 NFE exome

AF:

0.00170

AC:

1869

AN:

1101090

Gnomad4 Remaining exome

AF:

0.00151

AC:

AN:

59658

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00113

AC:

171

AN:

150760

Hom.:

Cov.:

AF XY:

0.000977

AC XY:

AN XY:

73668

show subpopulations

Gnomad4 AFR

AF:

0.000587

AC:

0.000586797

AN:

0.000586797

Gnomad4 AMR

AF:

0.000726

AC:

0.000726456

AN:

0.000726456

Gnomad4 ASJ

AF:

0.00551

AC:

0.00551364

AN:

0.00551364

Gnomad4 EAS

AF:

0.00155

AC:

0.00154979

AN:

0.00154979

Gnomad4 SAS

AF:

0.00105

AC:

0.00105219

AN:

0.00105219

Gnomad4 FIN

AF:

0.0000959

AC:

0.0000958589

AN:

0.0000958589

Gnomad4 NFE

AF:

0.00137

AC:

0.00137497

AN:

0.00137497

Gnomad4 OTH

AF:

0.00192

AC:

0.00191755

AN:

0.00191755

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00101

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VEZF1-related disorder

Benign:1

Mar 23, 2023

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

Mutation Taster

=80/20

polymorphism

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