Genetic Variant NM_033132.5:c.1173_1190delGCCGCCGCCGCCGCCGCC (chr13-99970413-TGGCGGCGGCGGCGGCGGC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_033132.5(ZIC5):c.1173_1190delGCCGCCGCCGCCGCCGCC(p.Pro392_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 0.000653 in 1,106,464 control chromosomes in the GnomAD database, including 112 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00067 ( 111 hom. )

Consequence

ZIC5
NM_033132.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 13-99970413-TGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chr13-99970413-TGGCGGCGGCGGCGGCGGC-T is described in ClinVar as Benign. ClinVar VariationId is 252765.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 62 AD gene.

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.1173_1190delGCCGCCGCCGCCGCCGCC	p.Pro392_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	NP_149123.3	Q96T25
	ZIC5	NR_146224.1		n.1479_1496delGCCGCCGCCGCCGCCGCC		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.1173_1190delGCCGCCGCCGCCGCCGCC	p.Pro392_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000267294.4	Q96T25
ENSG00000297638	ENST00000749511.1		n.135+304_135+321delGGCGGCGGCGGCGGCGGC		intron	N/A
ENSG00000297638	ENST00000749512.1		n.104+298_104+315delGGCGGCGGCGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000508

AC:

AN:

121980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000706

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000703

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00334

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000292

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000671

AC:

661

AN:

984384

Hom.:

111

AF XY:

0.000734

AC XY:

347

AN XY:

472480

show subpopulations

African (AFR)

AF:

0.000781

AC:

AN:

17932

American (AMR)

AF:

0.00249

AC:

AN:

6422

Ashkenazi Jewish (ASJ)

AF:

0.0000869

AC:

AN:

11504

East Asian (EAS)

AF:

0.00325

AC:

AN:

14460

South Asian (SAS)

AF:

0.00294

AC:

AN:

30954

European-Finnish (FIN)

AF:

0.000695

AC:

AN:

12950

Middle Eastern (MID)

AF:

0.000705

AC:

AN:

2838

European-Non Finnish (NFE)

AF:

0.000520

AC:

443

AN:

852568

Other (OTH)

AF:

0.00109

AC:

AN:

34756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000508

AC:

AN:

122080

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

AN XY:

59662

show subpopulations

African (AFR)

AF:

0.000704

AC:

AN:

35516

American (AMR)

AF:

0.000702

AC:

AN:

12826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2964

East Asian (EAS)

AF:

0.00335

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

3616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.000292

AC:

AN:

54766

Other (OTH)

AF:

0.00

AC:

AN:

1646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

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:

0.00

Hom.:

118

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=197/3

polymorphism

(source)

Splicing

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

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