Genetic Variant ZIC5:p.Pro397dup (chr13-99970413-T-TGGC) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_033132.5(ZIC5):c.1188_1190dupGCC(p.Pro397dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 181 hom., cov: 0)

Exomes 𝑓: 0.051 ( 812 hom. )

Consequence

ZIC5
NM_033132.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.56

Publications

9 publications found

Variant links:

Genes affected

ZIC5 (HGNC:20322): (Zic family member 5) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. The encoded protein may act as a transcriptional repressor. Studies in mouse and Xenopus support a role for this gene in neural crest development. Elevated expression of this gene has been observed in various human cancers and may contribute to cancer progression. This gene is closely linked to a related family member on chromosome 13. [provided by RefSeq, Mar 2017]

ZIC5 links:

ENSG00000297638 (HGNC:):

ENSG00000297638 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 13-99970413-T-TGGC is Benign according to our data. Variant chr13-99970413-T-TGGC is described in ClinVar as Benign. ClinVar VariationId is 252766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC5	NM_033132.5	MANE Select	c.1188_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	NP_149123.3	Q96T25
	ZIC5	NR_146224.1		n.1494_1496dupGCC		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZIC5	ENST00000267294.5	TSL:1 MANE Select	c.1188_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000267294.4	Q96T25
ENSG00000297638	ENST00000749511.1		n.135+319_135+321dupGGC		intron	N/A
ENSG00000297638	ENST00000749512.1		n.104+313_104+315dupGGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0489

AC:

5964

AN:

121926

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0358

Gnomad EAS

AF:

0.0217

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.0701

Gnomad MID

AF:

0.0563

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0479

GnomAD2 exomes

AF:

0.00153

AC:

AN:

60812

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00704

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0505

AC:

49702

AN:

984110

Hom.:

812

Cov.:

AF XY:

0.0492

AC XY:

23223

AN XY:

472334

show subpopulations

African (AFR)

AF:

0.0236

AC:

423

AN:

17932

American (AMR)

AF:

0.00436

AC:

AN:

6416

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

168

AN:

11502

East Asian (EAS)

AF:

0.00671

AC:

AN:

14458

South Asian (SAS)

AF:

0.0361

AC:

1117

AN:

30964

European-Finnish (FIN)

AF:

0.00325

AC:

AN:

12940

Middle Eastern (MID)

AF:

0.0250

AC:

AN:

2838

European-Non Finnish (NFE)

AF:

0.0542

AC:

46190

AN:

852314

Other (OTH)

AF:

0.0451

AC:

1566

AN:

34746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

2621

5242

7864

10485

13106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2394

4788

7182

9576

11970

<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:

0.0489

AC:

5973

AN:

122026

Hom.:

181

Cov.:

AF XY:

0.0485

AC XY:

2891

AN XY:

59640

show subpopulations

African (AFR)

AF:

0.0273

AC:

968

AN:

35502

American (AMR)

AF:

0.0334

AC:

428

AN:

12826

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

106

AN:

2964

East Asian (EAS)

AF:

0.0218

AC:

AN:

3586

South Asian (SAS)

AF:

0.0680

AC:

246

AN:

3616

European-Finnish (FIN)

AF:

0.0701

AC:

444

AN:

6338

Middle Eastern (MID)

AF:

0.0507

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.0657

AC:

3596

AN:

54728

Other (OTH)

AF:

0.0516

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

260

520

780

1040

1300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0154

Hom.:

118

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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