13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2
The NM_033132.5(ZIC5):c.1179_1190dupGCCGCCGCCGCC(p.Pro394_Pro397dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. 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.
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00016 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ZIC5
NM_033132.5 disruptive_inframe_insertion
NM_033132.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.56
Publications
9 publications found
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]
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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 29 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ZIC5 | NM_033132.5 | c.1179_1190dupGCCGCCGCCGCC | p.Pro394_Pro397dup | disruptive_inframe_insertion | Exon 1 of 2 | ENST00000267294.5 | NP_149123.3 | |
| ZIC5 | NR_146224.1 | n.1485_1496dupGCCGCCGCCGCC | non_coding_transcript_exon_variant | Exon 1 of 3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ZIC5 | ENST00000267294.5 | c.1179_1190dupGCCGCCGCCGCC | p.Pro394_Pro397dup | disruptive_inframe_insertion | Exon 1 of 2 | 1 | NM_033132.5 | ENSP00000267294.4 | ||
| ENSG00000297638 | ENST00000749511.1 | n.135+310_135+321dupGGCGGCGGCGGC | intron_variant | Intron 1 of 1 | ||||||
| ENSG00000297638 | ENST00000749512.1 | n.104+304_104+315dupGGCGGCGGCGGC | intron_variant | Intron 1 of 1 |
Frequencies
GnomAD3 genomes 0.000238 AC: 29AN: 121980Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
29
AN:
121980
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000155 AC: 153AN: 984558Hom.: 0 Cov.: 5 AF XY: 0.000171 AC XY: 81AN XY: 472570 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
153
AN:
984558
Hom.:
Cov.:
5
AF XY:
AC XY:
81
AN XY:
472570
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
17932
American (AMR)
AF:
AC:
0
AN:
6422
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
11504
East Asian (EAS)
AF:
AC:
4
AN:
14460
South Asian (SAS)
AF:
AC:
4
AN:
30970
European-Finnish (FIN)
AF:
AC:
0
AN:
12956
Middle Eastern (MID)
AF:
AC:
1
AN:
2840
European-Non Finnish (NFE)
AF:
AC:
139
AN:
852712
Other (OTH)
AF:
AC:
5
AN:
34762
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.376
Heterozygous variant carriers
0
8
17
25
34
42
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.000238 AC: 29AN: 122080Hom.: 0 Cov.: 0 AF XY: 0.000251 AC XY: 15AN XY: 59662 show subpopulations
GnomAD4 genome
AF:
AC:
29
AN:
122080
Hom.:
Cov.:
0
AF XY:
AC XY:
15
AN XY:
59662
show subpopulations
African (AFR)
AF:
AC:
4
AN:
35516
American (AMR)
AF:
AC:
1
AN:
12826
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2964
East Asian (EAS)
AF:
AC:
3
AN:
3586
South Asian (SAS)
AF:
AC:
1
AN:
3616
European-Finnish (FIN)
AF:
AC:
0
AN:
6340
Middle Eastern (MID)
AF:
AC:
0
AN:
138
European-Non Finnish (NFE)
AF:
AC:
20
AN:
54766
Other (OTH)
AF:
AC:
0
AN:
1646
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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