Genetic Variant ZIC5:p.Pro396_Pro397del (chr13-99970413-TGGCGGC-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 NM_033132.5(ZIC5):c.1185_1190delGCCGCC(p.Pro396_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 0.000784 in 1,098,634 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00075 ( 6 hom. )

Consequence

ZIC5
NM_033132.5 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 NM_033132.5

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.1185_1190delGCCGCC	p.Pro396_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.1491_1496delGCCGCC		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZIC5	ENST00000267294.5 link	c.1185_1190delGCCGCC	p.Pro396_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4	Q96T25
ENSG00000297638	ENST00000749511.1 link	n.135+316_135+321delGGCGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1 link	n.104+310_104+315delGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

126

AN:

121976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000860

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.000275

Gnomad FIN

AF:

0.00615

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000584

Gnomad OTH

AF:

0.000613

GnomAD4 exome

AF:

0.000754

AC:

736

AN:

976558

Hom.:

AF XY:

0.000841

AC XY:

394

AN XY:

468758

show subpopulations

African (AFR)

AF:

0.00259

AC:

AN:

16602

American (AMR)

AF:

0.00157

AC:

AN:

6354

Ashkenazi Jewish (ASJ)

AF:

0.000437

AC:

AN:

11438

East Asian (EAS)

AF:

0.000833

AC:

AN:

14412

South Asian (SAS)

AF:

0.000781

AC:

AN:

30742

European-Finnish (FIN)

AF:

0.00380

AC:

AN:

12904

Middle Eastern (MID)

AF:

0.00213

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.000662

AC:

561

AN:

846888

Other (OTH)

AF:

0.000756

AC:

AN:

34404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00102

AC:

125

AN:

122076

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

59658

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

35516

American (AMR)

AF:

0.000858

AC:

AN:

12826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2964

East Asian (EAS)

AF:

0.000279

AC:

AN:

3584

South Asian (SAS)

AF:

0.000277

AC:

AN:

3616

European-Finnish (FIN)

AF:

0.00615

AC:

AN:

6338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.000584

AC:

AN:

54766

Other (OTH)

AF:

0.000608

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=179/21

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-TGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over