17-57979243-T-TTGCTGCTGCTGC

Variant names:

• chr17-57979243-T-TTGCTGCTGCTGC
• rs57786397
• NM_007146.3:c.1035_1046dupGCAGCAGCAGCA

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_1046dupGCAGCAGCAGCA​(p.Gln346_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 0.000126 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 INS_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. Synonymous variant affecting the same amino acid position (i.e. Q349Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• 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 19 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_1046dupGCAGCAGCAGCA	p.Gln346_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1008_1019dupGCAGCAGCAGCA	p.Gln337_Gln340dup	disruptive_inframe_insertion	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_1046dupGCAGCAGCAGCA	p.Gln346_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.489_500dupGCAGCAGCAGCA	p.Gln164_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1176_1187dupGCAGCAGCAGCA	p.Gln393_Gln396dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 19 AN: 150648 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000115 AC: 166 AN: 1446302 Hom.: 0 Cov.: 32 AF XY: 0.000118 AC XY: 85 AN XY: 719520

African (AFR) AF: 0.000182 AC: 6 AN: 32926

American (AMR) AF: 0.000180 AC: 8 AN: 44324

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

East Asian (EAS) AF: 0.000204 AC: 8 AN: 39306

South Asian (SAS) AF: 0.000153 AC: 13 AN: 84798

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.000113 AC: 124 AN: 1101218

Other (OTH) AF: 0.0000838 AC: 5 AN: 59666

GnomAD4 genome AF: 0.000126 AC: 19 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.0000950 AC XY: 7 AN XY: 73668

African (AFR) AF: 0.000171 AC: 7 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: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.000210 AC: 1 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: 0.000103 AC: 7 AN: 67638

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

Alfa AF: 0.00 Hom.: 68

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41
Mutation Taster		=80/20	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;