chr17-57979243-TTGCTGCTGC-T

Variant names:

• chr17-57979243-TTGCTGCTGC-T
• rs57786397
• NM_007146.3:c.1038_1046delGCAGCAGCA

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_1046delGCAGCAGCA​(p.Gln347_Gln349del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00139 in 1,597,074 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: VEZF1 NM_007146.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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 -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007146.3
• BP6: Variant 17-57979243-TTGCTGCTGC-T is Benign according to our data. Variant chr17-57979243-TTGCTGCTGC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042684.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 172 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_1046delGCAGCAGCA	p.Gln347_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1011_1019delGCAGCAGCA	p.Gln338_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.1038_1046delGCAGCAGCA	p.Gln347_Gln349del	disruptive_inframe_deletion	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.492_500delGCAGCAGCA	p.Gln165_Gln167del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1179_1187delGCAGCAGCA	p.Gln394_Gln396del	disruptive_inframe_deletion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 172 AN: 150648 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000687

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000529

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00183

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.00142 AC: 2054 AN: 1446314 Hom.: 6 AF XY: 0.00139 AC XY: 999 AN XY: 719524

African (AFR) AF: 0.00109 AC: 36 AN: 32926

American (AMR) AF: 0.000767 AC: 34 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25812

East Asian (EAS) AF: 0.000382 AC: 15 AN: 39308

South Asian (SAS) AF: 0.00136 AC: 115 AN: 84798

European-Finnish (FIN) AF: 0.000266 AC: 14 AN: 52618

Middle Eastern (MID) AF: 0.000710 AC: 4 AN: 5636

European-Non Finnish (NFE) AF: 0.00160 AC: 1761 AN: 1101224

Other (OTH) AF: 0.00121 AC: 72 AN: 59666

GnomAD4 genome AF: 0.00114 AC: 172 AN: 150760 Hom.: 0 Cov.: 28 AF XY: 0.00110 AC XY: 81 AN XY: 73668

African (AFR) AF: 0.000685 AC: 28 AN: 40900

American (AMR) AF: 0.000528 AC: 8 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

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

South Asian (SAS) AF: 0.00126 AC: 6 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: 0.00183 AC: 124 AN: 67638

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

Alfa AF: 0.00 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		5.3
Mutation Taster		=184/16	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: COSV51969047; COSMIC: COSV51969047;