17-57979243-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr17-57979243-T-TTGCTGC
• rs57786397
• NM_007146.3:c.1041_1046dupGCAGCA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_007146.3(VEZF1):​c.1041_1046dupGCAGCA​(p.Gln348_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 0.0193 in 1,595,668 control chromosomes in the GnomAD database, including 252 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q349Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.014 (15 hom., cov: 28)
  • Exomes 𝑓: 0.020 (237 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter 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: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BP6: Variant 17-57979243-T-TTGCTGC is Benign according to our data. Variant chr17-57979243-T-TTGCTGC is described in ClinVar as Likely_benign. ClinVar VariationId is 3911283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2171/150742) while in subpopulation NFE AF = 0.0227 (1535/67630). AF 95% confidence interval is 0.0218. There are 15 homozygotes in GnomAd4. There are 991 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2171 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.1041_1046dupGCAGCA	p.Gln348_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1014_1019dupGCAGCA	p.Gln339_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.1041_1046dupGCAGCA	p.Gln348_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.495_500dupGCAGCA	p.Gln166_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1182_1187dupGCAGCA	p.Gln395_Gln396dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2169 AN: 150630 Hom.: 15 Cov.: 28

Gnomad AFR AF: 0.00902

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.00522

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00378

Gnomad FIN AF: 0.00853

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.00776

GnomAD4 exome AF: 0.0198 AC: 28676 AN: 1444926 Hom.: 237 Cov.: 32 AF XY: 0.0194 AC XY: 13934 AN XY: 718892

African (AFR) AF: 0.00851 AC: 280 AN: 32898

American (AMR) AF: 0.00666 AC: 295 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00624 AC: 161 AN: 25810

East Asian (EAS) AF: 0.000661 AC: 26 AN: 39308

South Asian (SAS) AF: 0.00537 AC: 455 AN: 84792

European-Finnish (FIN) AF: 0.0114 AC: 598 AN: 52610

Middle Eastern (MID) AF: 0.00727 AC: 41 AN: 5636

European-Non Finnish (NFE) AF: 0.0235 AC: 25849 AN: 1099918

Other (OTH) AF: 0.0163 AC: 971 AN: 59636

GnomAD4 genome AF: 0.0144 AC: 2171 AN: 150742 Hom.: 15 Cov.: 28 AF XY: 0.0135 AC XY: 991 AN XY: 73664

African (AFR) AF: 0.00905 AC: 370 AN: 40892

American (AMR) AF: 0.00707 AC: 107 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00522 AC: 18 AN: 3446

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.00379 AC: 18 AN: 4752

European-Finnish (FIN) AF: 0.00853 AC: 89 AN: 10432

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

European-Non Finnish (NFE) AF: 0.0227 AC: 1535 AN: 67630

Other (OTH) AF: 0.00768 AC: 16 AN: 2084

Alfa AF: 0.00770 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		0.41
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; COSMIC: COSV99365975; COSMIC: COSV99365975;