chr13-51950298-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PP5_Very_Strong
The NM_000053.4(ATP7B):c.2549C>T(p.Thr850Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T850T) has been classified as Likely benign.
Frequency
Consequence
NM_000053.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7B | NM_000053.4 | c.2549C>T | p.Thr850Ile | missense_variant | 10/21 | ENST00000242839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7B | ENST00000242839.10 | c.2549C>T | p.Thr850Ile | missense_variant | 10/21 | 1 | NM_000053.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249542Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135394
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
Wilson disease Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 28, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 16, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 18, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 850 of the ATP7B protein (p.Thr850Ile). This variant is present in population databases (rs777629392, gnomAD 0.01%). This missense change has been observed in individual(s) with Wilson disease (PMID: 21034864, 27398169, 29321352). ClinVar contains an entry for this variant (Variation ID: 554444). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 25, 2024 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 21, 2022 | PP3, PP4, PM2, PS4_moderate - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at