rs142998552
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000052.7(ATP7A):c.3153C>A(p.His1051Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,091 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H1051H) has been classified as Likely benign.
Frequency
Consequence
NM_000052.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.3153C>A | p.His1051Gln | missense_variant | 16/23 | ENST00000341514.11 | |
ATP7A | NM_001282224.2 | c.2919C>A | p.His973Gln | missense_variant | 15/22 | ||
ATP7A | NR_104109.2 | n.326C>A | non_coding_transcript_exon_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.3153C>A | p.His1051Gln | missense_variant | 16/23 | 1 | NM_000052.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000894 AC: 1AN: 111885Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34073
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097206Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362644
GnomAD4 genome ? AF: 0.00000894 AC: 1AN: 111885Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34073
ClinVar
Submissions by phenotype
Menkes kinky-hair syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 27, 2020 | - - |
Menkes kinky-hair syndrome;C0268353:Cutis laxa, X-linked;C1845359:X-linked distal spinal muscular atrophy type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces histidine with glutamine at codon 1051 of the ATP7A protein (p.His1051Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATP7A-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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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