NM_007146.3:c.1032_1046delGCAGCAGCAGCAGCA

Variant names:

• chr17-57979243-TTGCTGCTGCTGCTGC-T
• rs57786397
• NM_007146.3:c.1032_1046delGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_007146.3(VEZF1):​c.1032_1046delGCAGCAGCAGCAGCA​(p.Gln345_Gln349del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00308 in 1,597,004 control chromosomes in the GnomAD database, including 8 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0032 (8 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BP6: Variant 17-57979243-TTGCTGCTGCTGCTGC-T is Benign according to our data. Variant chr17-57979243-TTGCTGCTGCTGCTGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 330 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.1032_1046delGCAGCAGCAGCAGCA	p.Gln345_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1005_1019delGCAGCAGCAGCAGCA	p.Gln336_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.1032_1046delGCAGCAGCAGCAGCA	p.Gln345_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.486_500delGCAGCAGCAGCAGCA	p.Gln163_Gln167del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1173_1187delGCAGCAGCAGCAGCA	p.Gln392_Gln396del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 329 AN: 150642 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000981

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.000794

Gnomad ASJ AF: 0.00406

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00421

Gnomad FIN AF: 0.00173

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00145

GnomAD4 exome AF: 0.00317 AC: 4588 AN: 1446250 Hom.: 8 AF XY: 0.00314 AC XY: 2257 AN XY: 719484

African (AFR) AF: 0.000942 AC: 31 AN: 32924

American (AMR) AF: 0.00131 AC: 58 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00325 AC: 84 AN: 25810

East Asian (EAS) AF: 0.000407 AC: 16 AN: 39304

South Asian (SAS) AF: 0.00316 AC: 268 AN: 84784

European-Finnish (FIN) AF: 0.00110 AC: 58 AN: 52620

Middle Eastern (MID) AF: 0.00142 AC: 8 AN: 5636

European-Non Finnish (NFE) AF: 0.00356 AC: 3925 AN: 1101184

Other (OTH) AF: 0.00235 AC: 140 AN: 59664

GnomAD4 genome AF: 0.00219 AC: 330 AN: 150754 Hom.: 0 Cov.: 28 AF XY: 0.00200 AC XY: 147 AN XY: 73664

African (AFR) AF: 0.000978 AC: 40 AN: 40896

American (AMR) AF: 0.000792 AC: 12 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00406 AC: 14 AN: 3446

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

South Asian (SAS) AF: 0.00421 AC: 20 AN: 4752

European-Finnish (FIN) AF: 0.00173 AC: 18 AN: 10432

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00319 AC: 216 AN: 67636

Other (OTH) AF: 0.00144 AC: 3 AN: 2086

Alfa AF: 0.00130 Hom.: 68

Bravo AF: 0.00202

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	VEZF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=171/29	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: COSV51970420; COSMIC: COSV51970420;