Genetic Variant NM_007146.3:c.1032_1046dupGCAGCAGCAGCAGCA (chr17-57979243-T-TTGCTGCTGCTGCTGC) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_007146.3(VEZF1):c.1032_1046dupGCAGCAGCAGCAGCA(p.Gln345_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 0.000139 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 0.00014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000099 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VEZF1
NM_007146.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405

Publications

1 publications found

Variant links:

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

VEZF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 21 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_1046dupGCAGCAGCAGCAGCA	p.Gln345_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1005_1019dupGCAGCAGCAGCAGCA	p.Gln336_Gln340dup	disruptive_inframe_insertion	Exon 6 of 7	NP_001317322.1	J3QSH4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VEZF1	ENST00000581208.2	TSL:1 MANE Select	c.1032_1046dupGCAGCAGCAGCAGCA	p.Gln345_Gln349dup	disruptive_inframe_insertion	Exon 5 of 6	ENSP00000462337.1	Q14119
VEZF1	ENST00000258963.7	TSL:1	c.486_500dupGCAGCAGCAGCAGCA	p.Gln163_Gln167dup	disruptive_inframe_insertion	Exon 4 of 5	ENSP00000258963.3	J9JIC7
VEZF1	ENST00000905172.1		c.1173_1187dupGCAGCAGCAGCAGCA	p.Gln392_Gln396dup	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes

AF:

0.000139

AC:

AN:

150648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000989

AC:

143

AN:

1446320

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

719518

show subpopulations

African (AFR)

AF:

0.000364

AC:

AN:

32926

American (AMR)

AF:

0.000429

AC:

AN:

44324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39308

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84802

European-Finnish (FIN)

AF:

0.000133

AC:

AN:

52620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0000854

AC:

AN:

1101226

Other (OTH)

AF:

0.000134

AC:

AN:

59666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000139

AC:

AN:

150760

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73668

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

40900

American (AMR)

AF:

0.000132

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67638

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.41

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over