Variant rs10126585 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003413.4(ZIC3):c.912G>A(p.Arg304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,211,357 control chromosomes in the GnomAD database, including 4 homozygotes. There are 191 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., 82 hem., cov: 25)

Exomes 𝑓: 0.00034 ( 2 hom. 109 hem. )

Consequence

ZIC3
NM_003413.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.461

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant X-137567603-G-A is Benign according to our data. Variant chrX-137567603-G-A is described in ClinVar as [Benign]. Clinvar id is 239539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-137567603-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.461 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00289 (327/113116) while in subpopulation AFR AF= 0.0101 (315/31232). AF 95% confidence interval is 0.00917. There are 2 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZIC3	NM_003413.4 linkuse as main transcript	c.912G>A	p.Arg304=	synonymous_variant	1/3	ENST00000287538.10
ZIC3	NM_001330661.1 linkuse as main transcript	c.912G>A	p.Arg304=	synonymous_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZIC3	ENST00000287538.10 linkuse as main transcript	c.912G>A	p.Arg304=	synonymous_variant	1/3	1	NM_003413.4	P1	O60481-1
ZIC3	ENST00000370606.3 linkuse as main transcript	c.912G>A	p.Arg304=	synonymous_variant	1/3	5			O60481-2

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

327

AN:

113066

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

AN XY:

35208

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000923

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000650

GnomAD3 exomes

AF:

0.00106

AC:

194

AN:

183282

Hom.:

AF XY:

0.000737

AC XY:

AN XY:

67818

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.000693

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000341

AC:

375

AN:

1098241

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

109

AN XY:

363603

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000596

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.000412

GnomAD4 genome

AF:

0.00289

AC:

327

AN:

113116

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

AN XY:

35268

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.000922

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000642

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.00403

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

PreventionGenetics, part of Exact Sciences

- -

Heterotaxy, visceral, 1, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 20, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.0

DANN

Benign

0.91

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