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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The ENST00000287538.10(ZIC3):c.153_161dup(p.Ala53_Ala55dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,160,653 control chromosomes in the GnomAD database, including 1 homozygotes. There are 59 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.00013 ( 1 hom. 57 hem. )

Consequence

ZIC3
ENST00000287538.10 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

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 Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000287538.10

BP6

Variant X-137566825-A-ACGCCGCCGC is Benign according to our data. Variant chrX-137566825-A-ACGCCGCCGC is described in ClinVar as [Likely_benign]. Clinvar id is 3047546.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC3	NM_003413.4 linkuse as main transcript	c.153_161dup	p.Ala53_Ala55dup	inframe_insertion	1/3	ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1 linkuse as main transcript	c.153_161dup	p.Ala53_Ala55dup	inframe_insertion	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_161dup	p.Ala53_Ala55dup	inframe_insertion	1/3	1	NM_003413.4	ENSP00000287538	P1	O60481-1
ZIC3	ENST00000370606.3 linkuse as main transcript	c.153_161dup	p.Ala53_Ala55dup	inframe_insertion	1/3	5		ENSP00000359638		O60481-2

Frequencies

GnomAD3 genomes

AF:

0.0000984

AC:

AN:

111761

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34147

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000934

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00111

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000332

AC:

AN:

96477

Hom.:

AF XY:

0.000491

AC XY:

AN XY:

32583

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.0000539

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000134

AC:

141

AN:

1048849

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

341491

show subpopulations

Gnomad4 AFR exome

AF:

0.000200

Gnomad4 AMR exome

AF:

0.0000355

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000183

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000317

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

AF:

0.0000984

AC:

AN:

111804

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34200

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.0000932

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00112

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZIC3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2023

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