chr17-57979243-T-TTGCTGC

Variant names:

• chr17-57979243-T-TTGCTGC
• rs57786397
• NM_007146.3:c.1041_1046dupGCAGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_007146.3(VEZF1):​c.1041_1046dupGCAGCA​(p.Gln348_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 0.0193 in 1,595,668 control chromosomes in the GnomAD database, including 252 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (15 hom., cov: 28)
  • Exomes 𝑓: 0.020 (237 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
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2171/150742) while in subpopulation NFE AF= 0.0227 (1535/67630). AF 95% confidence interval is 0.0218. There are 15 homozygotes in gnomad4. There are 991 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1041_1046dupGCAGCA	p.Gln348_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.1041_1046dupGCAGCA	p.Gln348_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	1	NM_007146.3	ENSP00000462337.1
VEZF1	ENST00000258963.7	c.495_500dupGCAGCA	p.Gln166_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	1		ENSP00000258963.3
VEZF1	ENST00000584396.5	c.1014_1019dupGCAGCA	p.Gln339_Gln340dup	disruptive_inframe_insertion	Exon 5 of 6	5		ENSP00000464687.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2169 AN: 150630 Hom.: 15 Cov.: 28

Gnomad AFR AF: 0.00902

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.00522

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00378

Gnomad FIN AF: 0.00853

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.00776

GnomAD4 exome AF: 0.0198 AC: 28676 AN: 1444926 Hom.: 237 Cov.: 32 AF XY: 0.0194 AC XY: 13934 AN XY: 718892

Gnomad4 AFR exome AF: 0.00851

Gnomad4 AMR exome AF: 0.00666

Gnomad4 ASJ exome AF: 0.00624

Gnomad4 EAS exome AF: 0.000661

Gnomad4 SAS exome AF: 0.00537

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.0235

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0144 AC: 2171 AN: 150742 Hom.: 15 Cov.: 28 AF XY: 0.0135 AC XY: 991 AN XY: 73664

Gnomad4 AFR AF: 0.00905

Gnomad4 AMR AF: 0.00707

Gnomad4 ASJ AF: 0.00522

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.00379

Gnomad4 FIN AF: 0.00853

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.00768

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;