13-99970413-TGGCGGCGGCGGCGGCGGCGGC-T

Position:

• chr13-99970413-TGGCGGCGGCGGCGGCGGCGGC-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_033132.5(ZIC5):​c.1170_1190del​(p.Pro394_Pro400del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,106,640 control chromosomes in the GnomAD database, including 1,781 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0091 (1778 hom.)
• Consequence: ZIC5 NM_033132.5 inframe_deletion
• Clinical Significance: 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BP6: Variant 13-99970413-TGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chr13-99970413-TGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 713917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00909 (8952/984562) while in subpopulation SAS AF= 0.0476 (1473/30970). AF 95% confidence interval is 0.0455. There are 1778 homozygotes in gnomad4_exome. There are 4912 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 640 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1170_1190del	p.Pro394_Pro400del	inframe_deletion	1/2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1476_1496del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.1170_1190del	p.Pro394_Pro400del	inframe_deletion	1/2	1	NM_033132.5	ENSP00000267294	P1

Frequencies

GnomAD3 genomes AF: 0.00525 AC: 640 AN: 121978 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00594

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000556

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00268

Gnomad MID AF: 0.0352

Gnomad NFE AF: 0.00752

Gnomad OTH AF: 0.00552

GnomAD3 exomes AF: 0.0193 AC: 1175 AN: 60812 Hom.: 329 AF XY: 0.0191 AC XY: 708 AN XY: 37140

Gnomad AFR exome AF: 0.00686

Gnomad AMR exome AF: 0.0427

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.00206

Gnomad SAS exome AF: 0.0282

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0324

GnomAD4 exome AF: 0.00909 AC: 8952 AN: 984562 Hom.: 1778 AF XY: 0.0104 AC XY: 4912 AN XY: 472572

Gnomad4 AFR exome AF: 0.00184

Gnomad4 AMR exome AF: 0.0298

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.000484

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.00849

Gnomad4 NFE exome AF: 0.00742

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.00524 AC: 640 AN: 122078 Hom.: 3 Cov.: 0 AF XY: 0.00473 AC XY: 282 AN XY: 59662

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00593

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000558

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.00268

Gnomad4 NFE AF: 0.00752

Gnomad4 OTH AF: 0.00608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 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;