X-137566788-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003413.4(ZIC3):c.97G>T(p.Ala33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,178,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003413.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZIC3 | NM_003413.4 | c.97G>T | p.Ala33Ser | missense_variant | 1/3 | ENST00000287538.10 | NP_003404.1 | |
ZIC3 | NM_001330661.1 | c.97G>T | p.Ala33Ser | missense_variant | 1/3 | NP_001317590.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZIC3 | ENST00000287538.10 | c.97G>T | p.Ala33Ser | missense_variant | 1/3 | 1 | NM_003413.4 | ENSP00000287538 | P1 | |
ZIC3 | ENST00000370606.3 | c.97G>T | p.Ala33Ser | missense_variant | 1/3 | 5 | ENSP00000359638 |
Frequencies
GnomAD3 genomes AF: 0.000186 AC: 21AN: 113197Hom.: 0 Cov.: 25 AF XY: 0.000226 AC XY: 8AN XY: 35337
GnomAD3 exomes AF: 0.0000162 AC: 2AN: 123398Hom.: 0 AF XY: 0.0000258 AC XY: 1AN XY: 38764
GnomAD4 exome AF: 0.0000113 AC: 12AN: 1065512Hom.: 0 Cov.: 32 AF XY: 0.00000867 AC XY: 3AN XY: 345840
GnomAD4 genome AF: 0.000186 AC: 21AN: 113197Hom.: 0 Cov.: 25 AF XY: 0.000226 AC XY: 8AN XY: 35337
ClinVar
Submissions by phenotype
Heterotaxy, visceral, 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 06, 2021 | This sequence change replaces alanine with serine at codon 33 of the ZIC3 protein (p.Ala33Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with ZIC3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2023 | The c.97G>T (p.A33S) alteration is located in exon 1 (coding exon 1) of the ZIC3 gene. This alteration results from a G to T substitution at nucleotide position 97, causing the alanine (A) at amino acid position 33 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at