17-57979243-T-TTGCTGCTGC

Position:

• chr17-57979243-T-TTGCTGCTGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The ENST00000581208.2(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 ENST00000581208.2 disruptive_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.405

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 Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000581208.2
• 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/exons	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1038_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	5/6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEZF1	ENST00000581208.2	c.1038_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	5/6	1	NM_007146.3	ENSP00000462337.1
VEZF1	ENST00000258963.7	c.492_500dupGCAGCAGCA	p.Gln165_Gln167dup	disruptive_inframe_insertion	4/5	1		ENSP00000258963.3
VEZF1	ENST00000584396.5	c.1011_1019dupGCAGCAGCA	p.Gln338_Gln340dup	disruptive_inframe_insertion	5/6	5		ENSP00000464687.1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 171 AN: 150648 Hom.: 0 Cov.: 28

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.: 1 Cov.: 32 AF XY: 0.00158 AC XY: 1135 AN XY: 719462

Gnomad4 AFR exome AF: 0.000972

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.00473

Gnomad4 EAS exome AF: 0.00107

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.0000950

Gnomad4 NFE exome AF: 0.00170

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00113 AC: 171 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.000977 AC XY: 72 AN XY: 73668

Gnomad4 AFR AF: 0.000587

Gnomad4 AMR AF: 0.000726

Gnomad4 ASJ AF: 0.00551

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.0000959

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.00192

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

VEZF1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57786397; hg19: chr17-56056604;