17-57979243-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGC

Variant names:

• chr17-57979243-TTGCTGCTGCTGCTGCTGC-T
• rs57786397
• NM_007146.3:c.1029_1046delGCAGCAGCAGCAGCAGCA

Variant summary

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

The NM_007146.3(VEZF1):​c.1029_1046delGCAGCAGCAGCAGCAGCA​(p.Gln344_Gln349del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000259 in 150,760 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00043 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 39 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.1029_1046delGCAGCAGCAGCAGCAGCA	p.Gln344_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1002_1019delGCAGCAGCAGCAGCAGCA	p.Gln335_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.1029_1046delGCAGCAGCAGCAGCAGCA	p.Gln344_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.483_500delGCAGCAGCAGCAGCAGCA	p.Gln162_Gln167del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1170_1187delGCAGCAGCAGCAGCAGCA	p.Gln391_Gln396del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 39 AN: 150648 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000397

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000296

Gnomad OTH AF: 0.000484

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000432 AC: 625 AN: 1446324 Hom.: 1 AF XY: 0.000435 AC XY: 313 AN XY: 719528

African (AFR) AF: 0.000213 AC: 7 AN: 32926

American (AMR) AF: 0.000248 AC: 11 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00147 AC: 38 AN: 25810

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39308

South Asian (SAS) AF: 0.000637 AC: 54 AN: 84802

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

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5636

European-Non Finnish (NFE) AF: 0.000432 AC: 476 AN: 1101234

Other (OTH) AF: 0.000536 AC: 32 AN: 59666

GnomAD4 genome AF: 0.000259 AC: 39 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.000285 AC XY: 21 AN XY: 73668

African (AFR) AF: 0.000196 AC: 8 AN: 40900

American (AMR) AF: 0.000396 AC: 6 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.000580 AC: 2 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

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

European-Non Finnish (NFE) AF: 0.000296 AC: 20 AN: 67638

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 68

Bravo AF: 0.000336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=153/47	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;