Variant chr13-99970413-T-TGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_033132.5(ZIC5):c.1188_1190dupGCC(p.Pro397dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 181 hom., cov: 0)

Exomes 𝑓: 0.051 ( 812 hom. )

Consequence

ZIC5
NM_033132.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.56

Variant links:

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]

ZIC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_033132.5

BP6

Variant 13-99970413-T-TGGC is Benign according to our data. Variant chr13-99970413-T-TGGC is described in ClinVar as [Benign]. Clinvar id is 252766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.1188_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	1/2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.1494_1496dupGCC		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5 link	c.1188_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	1/2	1	NM_033132.5	ENSP00000267294.4		Q96T25

Frequencies

GnomAD3 genomes

AF:

0.0489

AC:

5964

AN:

121926

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0358

Gnomad EAS

AF:

0.0217

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.0701

Gnomad MID

AF:

0.0563

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0479

GnomAD3 exomes

AF:

0.00153

AC:

AN:

60812

Hom.:

AF XY:

0.00129

AC XY:

AN XY:

37140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.00704

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0505

AC:

49702

AN:

984110

Hom.:

812

Cov.:

AF XY:

0.0492

AC XY:

23223

AN XY:

472334

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.00671

Gnomad4 SAS exome

AF:

0.0361

Gnomad4 FIN exome

AF:

0.00325

Gnomad4 NFE exome

AF:

0.0542

Gnomad4 OTH exome

AF:

0.0451

GnomAD4 genome

AF:

0.0489

AC:

5973

AN:

122026

Hom.:

181

Cov.:

AF XY:

0.0485

AC XY:

2891

AN XY:

59640

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.0358

Gnomad4 EAS

AF:

0.0218

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.0701

Gnomad4 NFE

AF:

0.0657

Gnomad4 OTH

AF:

0.0516

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over