13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr13-99970413-T-TGGCGGC
• rs71114653
• NM_033132.5:c.1185_1190dupGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

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
• 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]

ENSG00000297638 (HGNC:):

ACMG classification

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 623 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1185_1190dupGCCGCC	p.Pro396_Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1491_1496dupGCCGCC		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.1185_1190dupGCCGCC	p.Pro396_Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+316_135+321dupGGCGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+310_104+315dupGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00508 AC: 620 AN: 121974 Hom.: 4 Cov.: 0

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

African (AFR) AF: 0.00363 AC: 65 AN: 17930

American (AMR) AF: 0.000779 AC: 5 AN: 6420

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 20 AN: 11504

East Asian (EAS) AF: 0.00249 AC: 36 AN: 14456

South Asian (SAS) AF: 0.00345 AC: 107 AN: 30972

European-Finnish (FIN) AF: 0.0000772 AC: 1 AN: 12956

Middle Eastern (MID) AF: 0.00317 AC: 9 AN: 2840

European-Non Finnish (NFE) AF: 0.00403 AC: 3438 AN: 852664

Other (OTH) AF: 0.00328 AC: 114 AN: 34764

GnomAD4 genome AF: 0.00510 AC: 623 AN: 122074 Hom.: 4 Cov.: 0 AF XY: 0.00479 AC XY: 286 AN XY: 59656

African (AFR) AF: 0.00425 AC: 151 AN: 35512

American (AMR) AF: 0.00561 AC: 72 AN: 12826

Ashkenazi Jewish (ASJ) AF: 0.00574 AC: 17 AN: 2964

East Asian (EAS) AF: 0.0131 AC: 47 AN: 3586

South Asian (SAS) AF: 0.00774 AC: 28 AN: 3616

European-Finnish (FIN) AF: 0.00189 AC: 12 AN: 6338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.00531 AC: 291 AN: 54766

Other (OTH) AF: 0.00304 AC: 5 AN: 1646

Alfa AF: 0.00144 Hom.: 118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=73/27	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71114653; hg19: chr13-100622667;