13-99970274-C-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_033132.5(ZIC5):āc.1330G>Cā(p.Glu444Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,784 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 30)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
ZIC5
NM_033132.5 missense
NM_033132.5 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.87
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17670691).
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152054Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251234Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727174
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152054Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74276
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2022 | The c.1402G>C (p.E468Q) alteration is located in exon 1 (coding exon 1) of the ZIC5 gene. This alteration results from a G to C substitution at nucleotide position 1402, causing the glutamic acid (E) at amino acid position 468 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at