Genetic Variant ZIC5:p.Pro395_Pro397del (chr13-99970413-TGGCGGCGGC-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_033132.5(ZIC5):c.1182_1190delGCCGCCGCC(p.Pro395_Pro397del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,106,596 control chromosomes in the GnomAD database, including 307 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 9 hom., cov: 0)

Exomes 𝑓: 0.0089 ( 298 hom. )

Consequence

ZIC5
NM_033132.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_033132.5

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0102 (1248/122066) while in subpopulation EAS AF = 0.0441 (158/3584). AF 95% confidence interval is 0.0385. There are 9 homozygotes in GnomAd4. There are 621 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 1248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.1182_1190delGCCGCCGCC	p.Pro395_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.1488_1496delGCCGCCGCC		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5 link	c.1182_1190delGCCGCCGCC	p.Pro395_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4		Q96T25

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1249

AN:

121966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.0442

Gnomad SAS

AF:

0.00660

Gnomad FIN

AF:

0.00205

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00986

Gnomad OTH

AF:

0.0160

GnomAD2 exomes

AF:

0.00109

AC:

AN:

60812

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.000515

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00894

AC:

8797

AN:

984530

Hom.:

298

AF XY:

0.00912

AC XY:

4309

AN XY:

472552

show subpopulations

Gnomad4 AFR exome

AF:

0.00424

AC:

AN:

17932

Gnomad4 AMR exome

AF:

0.0125

AC:

AN:

6420

Gnomad4 ASJ exome

AF:

0.0207

AC:

238

AN:

11502

Gnomad4 EAS exome

AF:

0.0350

AC:

506

AN:

14458

Gnomad4 SAS exome

AF:

0.00346

AC:

107

AN:

30966

Gnomad4 FIN exome

AF:

0.00100

AC:

AN:

12956

Gnomad4 NFE exome

AF:

0.00867

AC:

7395

AN:

852702

Gnomad4 Remaining exome

AF:

0.0104

AC:

361

AN:

34754

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.0102

AC:

1248

AN:

122066

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

621

AN XY:

59656

show subpopulations

Gnomad4 AFR

AF:

0.00535

AC:

0.0053497

AN:

0.0053497

Gnomad4 AMR

AF:

0.0167

AC:

0.0166849

AN:

0.0166849

Gnomad4 ASJ

AF:

0.0280

AC:

0.0280216

AN:

0.0280216

Gnomad4 EAS

AF:

0.0441

AC:

0.0440848

AN:

0.0440848

Gnomad4 SAS

AF:

0.00636

AC:

0.00636062

AN:

0.00636062

Gnomad4 FIN

AF:

0.00205

AC:

0.00205047

AN:

0.00205047

Gnomad4 NFE

AF:

0.00986

AC:

0.00986193

AN:

0.00986193

Gnomad4 OTH

AF:

0.0164

AC:

0.0164034

AN:

0.0164034

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00210

Hom.:

118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=180/20

polymorphism

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over