rs62637689
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003413.4(ZIC3):āc.162T>Cā(p.Ala54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,160,326 control chromosomes in the GnomAD database, including 15 homozygotes. There are 634 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0092 ( 7 hom., 313 hem., cov: 25)
Exomes š: 0.0012 ( 8 hom. 321 hem. )
Consequence
ZIC3
NM_003413.4 synonymous
NM_003413.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.87
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant X-137566853-T-C is Benign according to our data. Variant chrX-137566853-T-C is described in ClinVar as [Benign]. Clinvar id is 137958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-137566853-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.87 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00919 (1037/112782) while in subpopulation AFR AF= 0.0302 (942/31201). AF 95% confidence interval is 0.0286. There are 7 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZIC3 | NM_003413.4 | c.162T>C | p.Ala54= | synonymous_variant | 1/3 | ENST00000287538.10 | |
ZIC3 | NM_001330661.1 | c.162T>C | p.Ala54= | synonymous_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZIC3 | ENST00000287538.10 | c.162T>C | p.Ala54= | synonymous_variant | 1/3 | 1 | NM_003413.4 | P1 | |
ZIC3 | ENST00000370606.3 | c.162T>C | p.Ala54= | synonymous_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00917 AC: 1034AN: 112728Hom.: 7 Cov.: 25 AF XY: 0.00889 AC XY: 311AN XY: 34990
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GnomAD3 exomes AF: 0.00229 AC: 235AN: 102752Hom.: 5 AF XY: 0.00152 AC XY: 55AN XY: 36206
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GnomAD4 exome AF: 0.00116 AC: 1211AN: 1047544Hom.: 8 Cov.: 33 AF XY: 0.000940 AC XY: 321AN XY: 341514
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GnomAD4 genome ? AF: 0.00919 AC: 1037AN: 112782Hom.: 7 Cov.: 25 AF XY: 0.00893 AC XY: 313AN XY: 35054
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Heterotaxy, visceral, 1, X-linked Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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