Genetic Variant ZIC5:p.Pro388_Pro397del (chr13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-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.1161_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC(p.Pro388_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 0.0000132 in 984,586 control chromosomes in the GnomAD database, including 1 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: not found (cov: 0)

Exomes 𝑓: 0.000013 ( 1 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 GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.1161_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	p.Pro388_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.1467_1496delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC		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.1161_1190delGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	p.Pro388_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4	Q96T25
ENSG00000297638	ENST00000749511.1 link	n.135+292_135+321delGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1 link	n.104+286_104+315delGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000132

AC:

AN:

984586

Hom.:

AF XY:

0.0000169

AC XY:

AN XY:

472584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17932

American (AMR)

AF:

0.000156

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:

0.0000646

AC:

AN:

30972

European-Finnish (FIN)

AF:

0.0000772

AC:

AN:

12956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2840

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

852736

Other (OTH)

AF:

0.00

AC:

AN:

34764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.707

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Splicing

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

Publications

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13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over