13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGC

Position:

• chr13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_033132.5(ZIC5):​c.1176_1190del​(p.Pro396_Pro400del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,106,574 control chromosomes in the GnomAD database, including 1,047 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 0)
  • Exomes 𝑓: 0.010 (1038 hom.)
• Consequence: ZIC5 NM_033132.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BP6: Variant 13-99970413-TGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chr13-99970413-TGGCGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 787178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 883 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZIC5	NM_033132.5	c.1176_1190del	p.Pro396_Pro400del	inframe_deletion	1/2	ENST00000267294.5
ZIC5	NR_146224.1	n.1482_1496del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZIC5	ENST00000267294.5	c.1176_1190del	p.Pro396_Pro400del	inframe_deletion	1/2	1	NM_033132.5	P1

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 884 AN: 121968 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.00789

Gnomad ASJ AF: 0.000675

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.00275

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0352

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00736

GnomAD3 exomes AF: 0.00322 AC: 196 AN: 60812 Hom.: 17 AF XY: 0.00310 AC XY: 115 AN XY: 37140

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.000264

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000854

Gnomad FIN exome AF: 0.00426

Gnomad NFE exome AF: 0.00449

Gnomad OTH exome AF: 0.00711

GnomAD4 exome AF: 0.0104 AC: 10261 AN: 984506 Hom.: 1038 AF XY: 0.0108 AC XY: 5110 AN XY: 472550

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.00545

Gnomad4 ASJ exome AF: 0.000956

Gnomad4 EAS exome AF: 0.000622

Gnomad4 SAS exome AF: 0.00481

Gnomad4 FIN exome AF: 0.0191

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.00723 AC: 883 AN: 122068 Hom.: 9 Cov.: 0 AF XY: 0.00642 AC XY: 383 AN XY: 59656

Gnomad4 AFR AF: 0.00251

Gnomad4 AMR AF: 0.00780

Gnomad4 ASJ AF: 0.000675

Gnomad4 EAS AF: 0.00112

Gnomad4 SAS AF: 0.00277

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.00729

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71114653; hg19: chr13-100622667;