13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGC

Variant names:

• chr13-99970413-TGGCGGCGGCGGCGGCGGC-T
• rs71114653
• NM_033132.5:c.1173_1190delGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_033132.5(ZIC5):​c.1173_1190delGCCGCCGCCGCCGCCGCC​(p.Pro392_Pro397del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,106,464 control chromosomes in the GnomAD database, including 112 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00067 (111 hom.)
• Consequence: ZIC5 NM_033132.5 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BP6: Variant 13-99970413-TGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chr13-99970413-TGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 252765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1173_1190delGCCGCCGCCGCCGCCGCC	p.Pro392_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1479_1496delGCCGCCGCCGCCGCCGCC		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.1173_1190delGCCGCCGCCGCCGCCGCC	p.Pro392_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+304_135+321delGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+298_104+315delGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000508 AC: 62 AN: 121980 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000703

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00334

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000292

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000671 AC: 661 AN: 984384 Hom.: 111 AF XY: 0.000734 AC XY: 347 AN XY: 472480

African (AFR) AF: 0.000781 AC: 14 AN: 17932

American (AMR) AF: 0.00249 AC: 16 AN: 6422

Ashkenazi Jewish (ASJ) AF: 0.0000869 AC: 1 AN: 11504

East Asian (EAS) AF: 0.00325 AC: 47 AN: 14460

South Asian (SAS) AF: 0.00294 AC: 91 AN: 30954

European-Finnish (FIN) AF: 0.000695 AC: 9 AN: 12950

Middle Eastern (MID) AF: 0.000705 AC: 2 AN: 2838

European-Non Finnish (NFE) AF: 0.000520 AC: 443 AN: 852568

Other (OTH) AF: 0.00109 AC: 38 AN: 34756

GnomAD4 genome AF: 0.000508 AC: 62 AN: 122080 Hom.: 1 Cov.: 0 AF XY: 0.000603 AC XY: 36 AN XY: 59662

African (AFR) AF: 0.000704 AC: 25 AN: 35516

American (AMR) AF: 0.000702 AC: 9 AN: 12826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2964

East Asian (EAS) AF: 0.00335 AC: 12 AN: 3586

South Asian (SAS) AF: 0.00 AC: 0 AN: 3616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6340

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

European-Non Finnish (NFE) AF: 0.000292 AC: 16 AN: 54766

Other (OTH) AF: 0.00 AC: 0 AN: 1646

Alfa AF: 0.00 Hom.: 118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 05, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=197/3	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; COSMIC: COSV105860727;