3-147390969-C-G

Position:

chr3-147390969-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_032153.6(ZIC4):c.966G>C(p.Ser322Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,612,086 control chromosomes in the GnomAD database, including 1,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 108 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1281 hom. )

Consequence

ZIC4
NM_032153.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.690

Variant links:

Genes affected

ZIC4 (HGNC:20393): (Zic family member 4) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]

ZIC4 links:

ZIC4 (HGNC:):

ZIC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 3-147390969-C-G is Benign according to our data. Variant chr3-147390969-C-G is described in ClinVar as [Benign]. Clinvar id is 130789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0295 (4496/152334) while in subpopulation NFE AF= 0.0478 (3251/68032). AF 95% confidence interval is 0.0464. There are 108 homozygotes in gnomad4. There are 2091 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 108 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC4	NM_032153.6 linkuse as main transcript	c.966G>C	p.Ser322Ser	synonymous_variant	4/5	ENST00000383075.8	NP_115529.2	Q8N9L1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC4	ENST00000383075.8 linkuse as main transcript	c.966G>C	p.Ser322Ser	synonymous_variant	4/5	1	NM_032153.6	ENSP00000372553.3		Q8N9L1-1

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4499

AN:

152216

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00839

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0299

AC:

7231

AN:

241788

Hom.:

149

AF XY:

0.0309

AC XY:

4092

AN XY:

132390

show subpopulations

Gnomad AFR exome

AF:

0.00767

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.0482

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0388

AC:

56595

AN:

1459752

Hom.:

1281

Cov.:

AF XY:

0.0383

AC XY:

27814

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.00652

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0295

AC:

4496

AN:

152334

Hom.:

108

Cov.:

AF XY:

0.0281

AC XY:

2091

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00837

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0478

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.0294

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0476

EpiControl

AF:

0.0507

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.9

DANN

Benign

0.83

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