rs375788705
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_000052.7(ATP7A):āc.3863A>Gā(p.Gln1288Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,210,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000052.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.3863A>G | p.Gln1288Arg | missense_variant | 20/23 | ENST00000341514.11 | NP_000043.4 | |
ATP7A | NM_001282224.2 | c.3629A>G | p.Gln1210Arg | missense_variant | 19/22 | NP_001269153.1 | ||
ATP7A | NR_104109.2 | n.1036A>G | non_coding_transcript_exon_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.3863A>G | p.Gln1288Arg | missense_variant | 20/23 | 1 | NM_000052.7 | ENSP00000345728 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000356 AC: 4AN: 112262Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2AN XY: 34398
GnomAD3 exomes AF: 0.0000545 AC: 10AN: 183446Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67906
GnomAD4 exome AF: 0.0000519 AC: 57AN: 1098216Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 22AN XY: 363574
GnomAD4 genome AF: 0.0000356 AC: 4AN: 112262Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2AN XY: 34398
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2016 | The Q1288R variant in the ATP7A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q1288R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1288R variant is a semi-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Q1288R as a variant of uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | ATP7A: BS2; PGK1: BS2 - |
Menkes kinky-hair syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 11, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Menkes kinky-hair syndrome;C0268353:Cutis laxa, X-linked;C1845359:X-linked distal spinal muscular atrophy type 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at