rs398122850
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_003413.4(ZIC3):c.165_166insGCCGCC(p.Ala54_Ala55dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Benign.
Frequency
Genomes: not found (cov: 25)
Consequence
ZIC3
NM_003413.4 inframe_insertion
NM_003413.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003413.4.
PP5
Variant X-137566853-T-TGCCGCC is Pathogenic according to our data. Variant chrX-137566853-T-TGCCGCC is described in ClinVar as [Pathogenic]. Clinvar id is 29955.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ZIC3 | NM_003413.4 | c.165_166insGCCGCC | p.Ala54_Ala55dup | inframe_insertion | 1/3 | ENST00000287538.10 | |
| ZIC3 | NM_001330661.1 | c.165_166insGCCGCC | p.Ala54_Ala55dup | inframe_insertion | 1/3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ZIC3 | ENST00000287538.10 | c.165_166insGCCGCC | p.Ala54_Ala55dup | inframe_insertion | 1/3 | 1 | NM_003413.4 | P1 | |
| ZIC3 | ENST00000370606.3 | c.165_166insGCCGCC | p.Ala54_Ala55dup | inframe_insertion | 1/3 | 5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
25
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
25
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
VACTERL association, X-linked, with or without hydrocephalus Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at