Genetic Variant ZIC5:c.*326C>T (chr13-99965051-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033132.5(ZIC5):c.*326C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 141,360 control chromosomes in the GnomAD database, including 3,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3429 hom., cov: 24)

Exomes 𝑓: 0.21 ( 36 hom. )

Consequence

ZIC5
NM_033132.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.553

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5 link	c.*326C>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000267294.5	NP_149123.3	Q96T25
ZIC5	NR_146224.1 link	n.2713C>T	non_coding_transcript_exon_variant	Exon 3 of 3
ZIC5	NR_146225.2 link	n.982C>T	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5 link	c.*326C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_033132.5	ENSP00000267294.4		Q96T25

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

31119

AN:

139784

Hom.:

3427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.213

AC:

336

AN:

1576

Hom.:

Cov.:

AF XY:

0.215

AC XY:

199

AN XY:

924

show subpopulations

African (AFR)

AF:

0.625

AC:

AN:

American (AMR)

AF:

0.203

AC:

AN:

192

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.162

AC:

AN:

European-Finnish (FIN)

AF:

0.212

AC:

AN:

416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.223

AC:

184

AN:

826

Other (OTH)

AF:

0.233

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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

<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:

0.223

AC:

31119

AN:

139784

Hom.:

3429

Cov.:

AF XY:

0.223

AC XY:

15041

AN XY:

67464

show subpopulations

African (AFR)

AF:

0.224

AC:

8258

AN:

36880

American (AMR)

AF:

0.218

AC:

3027

AN:

13870

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

885

AN:

3416

East Asian (EAS)

AF:

0.103

AC:

505

AN:

4894

South Asian (SAS)

AF:

0.231

AC:

1028

AN:

4454

European-Finnish (FIN)

AF:

0.221

AC:

1631

AN:

7396

Middle Eastern (MID)

AF:

0.202

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.229

AC:

15110

AN:

65848

Other (OTH)

AF:

0.201

AC:

378

AN:

1876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1141

2281

3422

4562

5703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.220

Hom.:

6877

Bravo

AF:

0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.67

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over