chr17-57979243-TTGCTGCTGCTGC-T

Variant names:

• chr17-57979243-TTGCTGCTGCTGC-T
• rs57786397
• NM_007146.3:c.1035_1046delGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_007146.3(VEZF1):​c.1035_1046delGCAGCAGCAGCA​(p.Gln346_Gln349del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000818 in 1,597,060 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00082 (2 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.35
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BS2: High AC in GnomAd4 at 122 AD gene.

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.1035_1046delGCAGCAGCAGCA	p.Gln346_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1008_1019delGCAGCAGCAGCA	p.Gln337_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.1035_1046delGCAGCAGCAGCA	p.Gln346_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.489_500delGCAGCAGCAGCA	p.Gln164_Gln167del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1176_1187delGCAGCAGCAGCA	p.Gln393_Gln396del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.000810 AC: 122 AN: 150648 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000665

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000819 AC: 1185 AN: 1446300 Hom.: 2 AF XY: 0.000848 AC XY: 610 AN XY: 719506

African (AFR) AF: 0.00121 AC: 40 AN: 32924

American (AMR) AF: 0.000474 AC: 21 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25812

East Asian (EAS) AF: 0.000636 AC: 25 AN: 39308

South Asian (SAS) AF: 0.00243 AC: 206 AN: 84784

European-Finnish (FIN) AF: 0.0000570 AC: 3 AN: 52618

Middle Eastern (MID) AF: 0.00266 AC: 15 AN: 5634

European-Non Finnish (NFE) AF: 0.000740 AC: 815 AN: 1101230

Other (OTH) AF: 0.000989 AC: 59 AN: 59664

GnomAD4 genome AF: 0.000809 AC: 122 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.000787 AC XY: 58 AN XY: 73668

African (AFR) AF: 0.00164 AC: 67 AN: 40900

American (AMR) AF: 0.000198 AC: 3 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5162

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4752

European-Finnish (FIN) AF: 0.0000959 AC: 1 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000665 AC: 45 AN: 67638

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 68

Bravo AF: 0.000831

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=172/28	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs57786397; hg19: chr17-56056604;