Variant X-137566825-ACGCCGCCGCCGCCGC-ACGCCGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_003413.4(ZIC3):c.153_161del(p.Ala53_Ala55del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000669 in 1,160,670 control chromosomes in the GnomAD database, including 1 homozygotes. There are 229 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., 23 hem., cov: 24)

Exomes 𝑓: 0.00066 ( 1 hom. 206 hem. )

Consequence

ZIC3
NM_003413.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter U:3B:2

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

ZIC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003413.4

BP6

Variant X-137566825-ACGCCGCCGC-A is Benign according to our data. Variant chrX-137566825-ACGCCGCCGC-A is described in ClinVar as [Benign]. Clinvar id is 464970.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC3	NM_003413.4 linkuse as main transcript	c.153_161del	p.Ala53_Ala55del	inframe_deletion	1/3	ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1 linkuse as main transcript	c.153_161del	p.Ala53_Ala55del	inframe_deletion	1/3		NP_001317590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC3	ENST00000287538.10 linkuse as main transcript	c.153_161del	p.Ala53_Ala55del	inframe_deletion	1/3	1	NM_003413.4	ENSP00000287538	P1	O60481-1
ZIC3	ENST00000370606.3 linkuse as main transcript	c.153_161del	p.Ala53_Ala55del	inframe_deletion	1/3	5		ENSP00000359638		O60481-2

Frequencies

GnomAD3 genomes

AF:

0.000734

AC:

AN:

111758

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

AN XY:

34144

show subpopulations

Gnomad AFR

AF:

0.000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000934

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00171

Gnomad SAS

AF:

0.000742

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000605

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000829

AC:

AN:

96477

Hom.:

AF XY:

0.000921

AC XY:

AN XY:

32583

show subpopulations

Gnomad AFR exome

AF:

0.000793

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00330

Gnomad SAS exome

AF:

0.000378

Gnomad FIN exome

AF:

0.000162

Gnomad NFE exome

AF:

0.000672

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000664

AC:

696

AN:

1048869

Hom.:

AF XY:

0.000603

AC XY:

206

AN XY:

341511

show subpopulations

Gnomad4 AFR exome

AF:

0.000920

Gnomad4 AMR exome

AF:

0.000780

Gnomad4 ASJ exome

AF:

0.0000536

Gnomad4 EAS exome

AF:

0.00326

Gnomad4 SAS exome

AF:

0.000381

Gnomad4 FIN exome

AF:

0.000128

Gnomad4 NFE exome

AF:

0.000621

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000725

AC:

AN:

111801

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

AN XY:

34197

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00172

Gnomad4 SAS

AF:

0.000744

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000605

Gnomad4 OTH

AF:

0.00132

Bravo

AF:

0.000880

ClinVar

Significance: Benign

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Heterotaxy, visceral, 1, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 12, 2020

- -

ZIC3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 29, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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