NM_003413.4:c.159_161delCGC
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2
The NM_003413.4(ZIC3):c.159_161delCGC(p.Ala54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,155,920 control chromosomes in the GnomAD database, including 1 homozygotes. There are 149 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A53A) has been classified as Likely benign.
Frequency
Consequence
NM_003413.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZIC3 | ENST00000287538.10 | c.159_161delCGC | p.Ala54del | disruptive_inframe_deletion | Exon 1 of 3 | 1 | NM_003413.4 | ENSP00000287538.5 | ||
ZIC3 | ENST00000370606.3 | c.159_161delCGC | p.Ala54del | disruptive_inframe_deletion | Exon 1 of 3 | 5 | ENSP00000359638.3 | |||
LINC02931 | ENST00000786828.1 | n.130+2246_130+2248delGCG | intron_variant | Intron 1 of 5 |
Frequencies
GnomAD3 genomes AF: 0.000143 AC: 16AN: 111747Hom.: 0 Cov.: 24 show subpopulations
GnomAD2 exomes AF: 0.00104 AC: 100AN: 96477 AF XY: 0.000982 show subpopulations
GnomAD4 exome AF: 0.000330 AC: 345AN: 1044131Hom.: 1 AF XY: 0.000417 AC XY: 141AN XY: 338231 show subpopulations
GnomAD4 genome AF: 0.000152 AC: 17AN: 111789Hom.: 0 Cov.: 24 AF XY: 0.000234 AC XY: 8AN XY: 34195 show subpopulations
ClinVar
Submissions by phenotype
Heterotaxy, visceral, 1, X-linked Uncertain:1Benign:1
This variant, c.159_161del, results in the deletion of 1 amino acid(s) of the ZIC3 protein (p.Ala55del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ZIC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 573248). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
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ZIC3-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at