17-57979243-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr17-57979243-T-TTGCTGCTGC
• rs57786397
• NM_007146.3:c.1038_1046dupGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_007146.3(VEZF1):​c.1038_1046dupGCAGCAGCA​(p.Gln347_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 0.00113 in 150,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. Q349Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0016 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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 -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BP6: Variant 17-57979243-T-TTGCTGCTGC is Benign according to our data. Variant chr17-57979243-T-TTGCTGCTGC is described in ClinVar as Likely_benign. ClinVar VariationId is 3033431.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 171 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.1038_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1011_1019dupGCAGCAGCA	p.Gln338_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.1038_1046dupGCAGCAGCA	p.Gln347_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.492_500dupGCAGCAGCA	p.Gln165_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1179_1187dupGCAGCAGCA	p.Gln394_Gln396dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 171 AN: 150648 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000588

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.000727

Gnomad ASJ AF: 0.00551

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00194

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00159 AC: 2303 AN: 1446168 Hom.: 1 Cov.: 32 AF XY: 0.00158 AC XY: 1135 AN XY: 719462

African (AFR) AF: 0.000972 AC: 32 AN: 32926

American (AMR) AF: 0.00120 AC: 53 AN: 44322

Ashkenazi Jewish (ASJ) AF: 0.00473 AC: 122 AN: 25812

East Asian (EAS) AF: 0.00107 AC: 42 AN: 39304

South Asian (SAS) AF: 0.00101 AC: 86 AN: 84802

European-Finnish (FIN) AF: 0.0000950 AC: 5 AN: 52620

Middle Eastern (MID) AF: 0.000710 AC: 4 AN: 5634

European-Non Finnish (NFE) AF: 0.00170 AC: 1869 AN: 1101090

Other (OTH) AF: 0.00151 AC: 90 AN: 59658

GnomAD4 genome AF: 0.00113 AC: 171 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.000977 AC XY: 72 AN XY: 73668

African (AFR) AF: 0.000587 AC: 24 AN: 40900

American (AMR) AF: 0.000726 AC: 11 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00551 AC: 19 AN: 3446

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5162

South Asian (SAS) AF: 0.00105 AC: 5 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: 0.00137 AC: 93 AN: 67638

Other (OTH) AF: 0.00192 AC: 4 AN: 2086

Alfa AF: 0.00101 Hom.: 68

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	VEZF1-related disorder (1)

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;