17-57979243-T-C

Position:

• chr17-57979243-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_007146.3(VEZF1):​c.1047A>G​(p.Gln349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00088 in 1,596,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00089 (1 hom.)
• Consequence: VEZF1 NM_007146.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.805

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-57979243-T-C is Benign according to our data. Variant chr17-57979243-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 728195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.805 with no splicing effect.
• BS2: High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1047A>G	p.Gln349=	synonymous_variant	5/6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEZF1	ENST00000581208.2	c.1047A>G	p.Gln349=	synonymous_variant	5/6	1	NM_007146.3	ENSP00000462337	P2
VEZF1	ENST00000258963.7	c.504A>G	p.Gln168=	synonymous_variant	4/5	1		ENSP00000258963
VEZF1	ENST00000584396.5	c.1020A>G	p.Gln340=	synonymous_variant	5/6	5		ENSP00000464687	A2

Frequencies

GnomAD3 genomes AF: 0.000783 AC: 118 AN: 150648 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000687

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.000891 AC: 1288 AN: 1446204 Hom.: 1 Cov.: 32 AF XY: 0.000955 AC XY: 687 AN XY: 719454

Gnomad4 AFR exome AF: 0.000729

Gnomad4 AMR exome AF: 0.000699

Gnomad4 ASJ exome AF: 0.00101

Gnomad4 EAS exome AF: 0.000178

Gnomad4 SAS exome AF: 0.000248

Gnomad4 FIN exome AF: 0.000152

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.000788

GnomAD4 genome AF: 0.000783 AC: 118 AN: 150760 Hom.: 0 Cov.: 29 AF XY: 0.000611 AC XY: 45 AN XY: 73668

Gnomad4 AFR AF: 0.000685

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000288

Gnomad4 NFE AF: 0.00117

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00196 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.15
DANN	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs138088904; hg19: chr17-56056604; COSMIC: COSV51967854; COSMIC: COSV51967854;