3-147396072-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_032153.6(ZIC4):c.468G>A(p.Thr156Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000904 in 1,614,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ZIC4
NM_032153.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108

Publications

1 publications found

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:

ZIC1 (HGNC:12872): (Zic family member 1) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development. Aberrant expression of this gene is seen in medulloblastoma, a childhood brain tumor. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 4, a related family member on chromosome 3. This gene encodes a transcription factor that can bind and transactivate the apolipoprotein E gene. [provided by RefSeq, Jul 2008]

ZIC1 Gene-Disease associations (from GenCC):

craniosynostosis 6
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
structural brain anomalies with impaired intellectual development and craniosynostosis
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
isolated brachycephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated oxycephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated plagiocephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Dandy-Walker syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZIC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-147396072-C-T is Benign according to our data. Variant chr3-147396072-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2059461.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.108 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032153.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZIC4	NM_032153.6	MANE Select	c.468G>A	p.Thr156Thr	synonymous	Exon 3 of 5	NP_115529.2
ZIC4	NM_001168378.1		c.618G>A	p.Thr206Thr	synonymous	Exon 3 of 5	NP_001161850.1	Q8N9L1-3
ZIC4	NM_001168379.2		c.582G>A	p.Thr194Thr	synonymous	Exon 3 of 5	NP_001161851.1	Q8N9L1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZIC4	ENST00000383075.8	TSL:1 MANE Select	c.468G>A	p.Thr156Thr	synonymous	Exon 3 of 5	ENSP00000372553.3	Q8N9L1-1
ZIC4	ENST00000462748.6	TSL:1	c.468G>A	p.Thr156Thr	synonymous	Exon 3 of 3	ENSP00000420627.2	C9JD04
ZIC4	ENST00000525172.6	TSL:2	c.618G>A	p.Thr206Thr	synonymous	Exon 3 of 5	ENSP00000435509.2	Q8N9L1-3

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

251346

AF XY:

0.0000809

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112012

Other (OTH)

AF:

0.0000828

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000518

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00187

AC:

AN:

41602

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000461

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.3

(source)

DANN

Benign

0.96

PhyloP100

0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over