17-57979243-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr17-57979243-T-TTGC
• rs57786397
• NM_007146.3:c.1044_1046dupGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BA1

The NM_007146.3(VEZF1):​c.1044_1046dupGCA​(p.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 0.108 in 1,591,096 control chromosomes in the GnomAD database, including 6,049 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q349Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.11 (917 hom., cov: 28)
  • Exomes 𝑓: 0.11 (5132 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1044_1046dupGCA	p.Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEZF1	ENST00000581208.2	c.1044_1046dupGCA	p.Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	1	NM_007146.3	ENSP00000462337.1
VEZF1	ENST00000258963.7	c.498_500dupGCA	p.Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	1		ENSP00000258963.3
VEZF1	ENST00000584396.5	c.1017_1019dupGCA	p.Gln340dup	disruptive_inframe_insertion	Exon 5 of 6	5		ENSP00000464687.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16587 AN: 150584 Hom.: 916 Cov.: 28

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.108 AC: 155640 AN: 1440400 Hom.: 5132 Cov.: 32 AF XY: 0.108 AC XY: 77060 AN XY: 716616

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0567

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0232

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.0771

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.110 AC: 16588 AN: 150696 Hom.: 917 Cov.: 28 AF XY: 0.105 AC XY: 7723 AN XY: 73638

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.0771

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.105

ClinVar

Not reported in ClinVar

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;