Variant chr13-99970413-TGGC-T 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_1190delGCC(p.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 0.202 in 1,099,906 control chromosomes in the GnomAD database, including 26,305 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10159 hom., cov: 0)

Exomes 𝑓: 0.18 ( 16146 hom. )

Consequence

ZIC5
NM_033132.5 disruptive_inframe_deletion

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-TGGC-T is Benign according to our data. Variant chr13-99970413-TGGC-T is described in ClinVar as [Benign]. Clinvar id is 403621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-99970413-TGGC-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.1188_1190delGCC	p.Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.1494_1496delGCC		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 link	c.1188_1190delGCC	p.Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4		Q96T25

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

45311

AN:

121798

Hom.:

10139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.0131

AC:

796

AN:

60812

Hom.:

107

AF XY:

0.0114

AC XY:

424

AN XY:

37140

show subpopulations

Gnomad AFR exome

AF:

0.00810

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00528

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.0457

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.00632

GnomAD4 exome

AF:

0.180

AC:

176352

AN:

978006

Hom.:

16146

AF XY:

0.177

AC XY:

82953

AN XY:

469078

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.0894

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0643

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0549

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.372

AC:

45384

AN:

121900

Hom.:

10159

Cov.:

AF XY:

0.371

AC XY:

22088

AN XY:

59580

show subpopulations

Gnomad4 AFR

AF:

0.666

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.318

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

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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