Genetic Variant ZIC5:p.Pro389_Pro397del (chr13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGC-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

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

The ENST00000267294.5(ZIC5):c.1164_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCC(p.Pro389_Pro397del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000361 in 1,106,666 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000037 ( 8 hom. )

Consequence

ZIC5
ENST00000267294.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56

Publications

9 publications found

Variant links:

Genes affected

ZIC5 (HGNC:20322): (Zic family member 5) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. The encoded protein may act as a transcriptional repressor. Studies in mouse and Xenopus support a role for this gene in neural crest development. Elevated expression of this gene has been observed in various human cancers and may contribute to cancer progression. This gene is closely linked to a related family member on chromosome 13. [provided by RefSeq, Mar 2017]

ZIC5 links:

ENSG00000297638 (HGNC:):

ENSG00000297638 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000267294.5

BS2

High AC in GnomAdExome4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000267294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC5	NM_033132.5	MANE Select	c.1164_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCC	p.Pro389_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	NP_149123.3
	ZIC5	NR_146224.1		n.1470_1496delGCCGCCGCCGCCGCCGCCGCCGCCGCC		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZIC5	ENST00000267294.5	TSL:1 MANE Select	c.1164_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCC	p.Pro389_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1		n.135+295_135+321delGGCGGCGGCGGCGGCGGCGGCGGCGGC		intron	N/A
ENSG00000297638	ENST00000749512.1		n.104+289_104+315delGGCGGCGGCGGCGGCGGCGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

121980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000183

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000366

AC:

AN:

984586

Hom.:

AF XY:

0.0000423

AC XY:

AN XY:

472584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17932

American (AMR)

AF:

0.00

AC:

AN:

6422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11504

East Asian (EAS)

AF:

0.000138

AC:

AN:

14460

South Asian (SAS)

AF:

0.000161

AC:

AN:

30972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2840

European-Non Finnish (NFE)

AF:

0.0000293

AC:

AN:

852736

Other (OTH)

AF:

0.000115

AC:

AN:

34764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.660

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000328

AC:

AN:

122080

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

59662

show subpopulations

African (AFR)

AF:

0.0000563

AC:

AN:

35516

American (AMR)

AF:

0.00

AC:

AN:

12826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2964

East Asian (EAS)

AF:

0.000279

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

3616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.0000183

AC:

AN:

54766

Other (OTH)

AF:

0.00

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=177/23

polymorphism

(source)

Splicing

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

Publications

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13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over