17-57979243-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr17-57979243-TTGC-T
• rs57786397
• NM_007146.3:c.1044_1046delGCA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_007146.3(VEZF1):​c.1044_1046delGCA​(p.Gln349del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,584,348 control chromosomes in the GnomAD database, including 272 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (143 hom., cov: 28)
  • Exomes 𝑓: 0.0099 (129 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.478
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• cardiomyopathy, dilated, 100

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BP6: Variant 17-57979243-TTGC-T is Benign according to our data. Variant chr17-57979243-TTGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3911280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007146.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZF1	NM_007146.3	MANE Select	c.1044_1046delGCA	p.Gln349del	disruptive_inframe_deletion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1017_1019delGCA	p.Gln340del	disruptive_inframe_deletion	Exon 6 of 7	NP_001317322.1	J3QSH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZF1	ENST00000581208.2	TSL:1 MANE Select	c.1044_1046delGCA	p.Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.498_500delGCA	p.Gln167del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1185_1187delGCA	p.Gln396del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4341 AN: 150604 Hom.: 143 Cov.: 28

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00377

Gnomad EAS AF: 0.00947

Gnomad SAS AF: 0.00463

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00893

Gnomad OTH AF: 0.0155

GnomAD4 exome AF: 0.00993 AC: 14231 AN: 1433632 Hom.: 129 AF XY: 0.00956 AC XY: 6817 AN XY: 713114

African (AFR) AF: 0.0824 AC: 2667 AN: 32378

American (AMR) AF: 0.00834 AC: 364 AN: 43660

Ashkenazi Jewish (ASJ) AF: 0.00243 AC: 62 AN: 25464

East Asian (EAS) AF: 0.00647 AC: 249 AN: 38478

South Asian (SAS) AF: 0.00524 AC: 438 AN: 83538

European-Finnish (FIN) AF: 0.00966 AC: 500 AN: 51772

Middle Eastern (MID) AF: 0.00966 AC: 54 AN: 5588

European-Non Finnish (NFE) AF: 0.00838 AC: 9171 AN: 1093756

Other (OTH) AF: 0.0123 AC: 726 AN: 58998

GnomAD4 genome AF: 0.0288 AC: 4344 AN: 150716 Hom.: 143 Cov.: 28 AF XY: 0.0279 AC XY: 2052 AN XY: 73646

African (AFR) AF: 0.0820 AC: 3353 AN: 40868

American (AMR) AF: 0.0104 AC: 157 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 13 AN: 3446

East Asian (EAS) AF: 0.00950 AC: 49 AN: 5160

South Asian (SAS) AF: 0.00463 AC: 22 AN: 4750

European-Finnish (FIN) AF: 0.0105 AC: 110 AN: 10428

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00895 AC: 605 AN: 67634

Other (OTH) AF: 0.0153 AC: 32 AN: 2086

Alfa AF: 0.00926 Hom.: 68

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48
Mutation Taster		=83/17	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs57786397;

hg19: chr17-56056604;

COSMIC: COSV51968229;

COSMIC: COSV51968229;