13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_033132.5(ZIC5):​c.1185_1190dupGCCGCC​(p.Pro396_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 0.0051 ( 4 hom., cov: 0)
Exomes 𝑓: 0.0039 ( 5 hom. )

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]

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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 623 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZIC5NM_033132.5 linkc.1185_1190dupGCCGCC p.Pro396_Pro397dup disruptive_inframe_insertion 1/2 ENST00000267294.5 NP_149123.3 Q96T25
ZIC5NR_146224.1 linkn.1491_1496dupGCCGCC non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZIC5ENST00000267294.5 linkc.1185_1190dupGCCGCC p.Pro396_Pro397dup disruptive_inframe_insertion 1/21 NM_033132.5 ENSP00000267294.4 Q96T25

Frequencies

GnomAD3 genomes
AF:
0.00508
AC:
620
AN:
121974
Hom.:
4
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00421
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00563
Gnomad ASJ
AF:
0.00574
Gnomad EAS
AF:
0.0131
Gnomad SAS
AF:
0.00771
Gnomad FIN
AF:
0.00189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00531
Gnomad OTH
AF:
0.00245
GnomAD4 exome
AF:
0.00385
AC:
3795
AN:
984506
Hom.:
5
Cov.:
5
AF XY:
0.00378
AC XY:
1785
AN XY:
472538
show subpopulations
Gnomad4 AFR exome
AF:
0.00363
Gnomad4 AMR exome
AF:
0.000779
Gnomad4 ASJ exome
AF:
0.00174
Gnomad4 EAS exome
AF:
0.00249
Gnomad4 SAS exome
AF:
0.00345
Gnomad4 FIN exome
AF:
0.0000772
Gnomad4 NFE exome
AF:
0.00403
Gnomad4 OTH exome
AF:
0.00328
GnomAD4 genome
AF:
0.00510
AC:
623
AN:
122074
Hom.:
4
Cov.:
0
AF XY:
0.00479
AC XY:
286
AN XY:
59656
show subpopulations
Gnomad4 AFR
AF:
0.00425
Gnomad4 AMR
AF:
0.00561
Gnomad4 ASJ
AF:
0.00574
Gnomad4 EAS
AF:
0.0131
Gnomad4 SAS
AF:
0.00774
Gnomad4 FIN
AF:
0.00189
Gnomad4 NFE
AF:
0.00531
Gnomad4 OTH
AF:
0.00304

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