chr13-99970413-TGGCGGCGGCGGCGGCGGC-T

Position:

• chr13-99970413-TGGCGGCGGCGGCGGCGGC-T

Variant summary

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

The NM_033132.5(ZIC5):​c.1173_1190del​(p.Pro395_Pro400del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,106,464 control chromosomes in the GnomAD database, including 112 homozygotes. 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 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 -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/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1173_1190del	p.Pro395_Pro400del	inframe_deletion	1/2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1479_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.1173_1190del	p.Pro395_Pro400del	inframe_deletion	1/2	1	NM_033132.5	ENSP00000267294	P1

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

Gnomad4 AFR exome AF: 0.000781

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.0000869

Gnomad4 EAS exome AF: 0.00325

Gnomad4 SAS exome AF: 0.00294

Gnomad4 FIN exome AF: 0.000695

Gnomad4 NFE exome AF: 0.000520

Gnomad4 OTH exome AF: 0.00109

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

Gnomad4 AFR AF: 0.000704

Gnomad4 AMR AF: 0.000702

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00335

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000292

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Aug 05, 2015

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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;