rs1557237081
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000052.7(ATP7A):c.3289A>C(p.Lys1097Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,094,842 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000052.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.3289A>C | p.Lys1097Gln | missense_variant | Exon 16 of 23 | ENST00000341514.11 | NP_000043.4 | |
ATP7A | NM_001282224.2 | c.3055A>C | p.Lys1019Gln | missense_variant | Exon 15 of 22 | NP_001269153.1 | ||
ATP7A | NR_104109.2 | n.462A>C | non_coding_transcript_exon_variant | Exon 3 of 10 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1094842Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 360396
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Menkes kinky-hair syndrome;C0268353:Cutis laxa, X-linked;C1845359:X-linked distal spinal muscular atrophy type 3 Uncertain:1
This sequence change replaces lysine with glutamine at codon 1097of the ATP7A protein (p.Lys1097Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. 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: "Possibly Damaging"; 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. This variant has not been reported in the literature in individuals with ATP7A-related disease. ClinVar contains an entry for this variant (Variation ID: 533672). This variant is not present in population databases (ExAC no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at