rs773385516
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000053.4(ATP7B):c.1568T>C(p.Leu523Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.1568T>C | p.Leu523Ser | missense_variant | Exon 4 of 21 | ENST00000242839.10 | NP_000044.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135306
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Wilson disease Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 523 of the ATP7B protein (p.Leu523Ser). This variant is present in population databases (rs773385516, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at