13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -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. 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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
ZIC5NM_033132.5 linkc.1179_1190dupGCCGCCGCCGCC p.Pro394_Pro397dup disruptive_inframe_insertion Exon 1 of 2 ENST00000267294.5 NP_149123.3 Q96T25
ZIC5NR_146224.1 linkn.1485_1496dupGCCGCCGCCGCC non_coding_transcript_exon_variant Exon 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZIC5ENST00000267294.5 linkc.1179_1190dupGCCGCCGCCGCC p.Pro394_Pro397dup disruptive_inframe_insertion Exon 1 of 2 1 NM_033132.5 ENSP00000267294.4 Q96T25

Frequencies

GnomAD3 genomes
AF:
0.000238
AC:
29
AN:
121980
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000113
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000781
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000834
Gnomad SAS
AF:
0.000275
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000365
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000155
AC:
153
AN:
984558
Hom.:
0
Cov.:
5
AF XY:
0.000171
AC XY:
81
AN XY:
472570
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000277
Gnomad4 SAS exome
AF:
0.000129
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000163
Gnomad4 OTH exome
AF:
0.000144
GnomAD4 genome
AF:
0.000238
AC:
29
AN:
122080
Hom.:
0
Cov.:
0
AF XY:
0.000251
AC XY:
15
AN XY:
59662
show subpopulations
Gnomad4 AFR
AF:
0.000113
Gnomad4 AMR
AF:
0.0000780
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000837
Gnomad4 SAS
AF:
0.000277
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000365
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs71114653; hg19: chr13-100622667; API