rs1557231581
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000052.7(ATP7A):āc.219T>Cā(p.Ala73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,206,536 control chromosomes in the GnomAD database, including 2 homozygotes. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes š: 0.000016 ( 2 hom. 4 hem. )
Consequence
ATP7A
NM_000052.7 synonymous
NM_000052.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0230
Genes affected
ATP7A (HGNC:869): (ATPase copper transporting alpha) This gene encodes a transmembrane protein that functions in copper transport across membranes. This protein is localized to the trans Golgi network, where it is predicted to supply copper to copper-dependent enzymes in the secretory pathway. It relocalizes to the plasma membrane under conditions of elevated extracellular copper, and functions in the efflux of copper from cells. Mutations in this gene are associated with Menkes disease, X-linked distal spinal muscular atrophy, and occipital horn syndrome. Alternatively-spliced transcript variants have been observed. [provided by RefSeq, Aug 2013]
PGK1 (HGNC:8896): (phosphoglycerate kinase 1) The protein encoded by this gene is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. The encoded protein may also act as a cofactor for polymerase alpha. Additionally, this protein is secreted by tumor cells where it participates in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which consequently leads to the release of the tumor blood vessel inhibitor angiostatin. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Deficiency of the enzyme is associated with a wide range of clinical phenotypes hemolytic anemia and neurological impairment. Pseudogenes of this gene have been defined on chromosomes 19, 21 and the X chromosome. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant X-77988340-T-C is Benign according to our data. Variant chrX-77988340-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 533687.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.023 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.219T>C | p.Ala73= | synonymous_variant | 3/23 | ENST00000341514.11 | |
ATP7A | NM_001282224.2 | c.219T>C | p.Ala73= | synonymous_variant | 3/22 | ||
ATP7A | NR_104109.2 | n.284+16579T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.219T>C | p.Ala73= | synonymous_variant | 3/23 | 1 | NM_000052.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000895 AC: 1AN: 111689Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33859
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GnomAD3 exomes AF: 0.00000558 AC: 1AN: 179190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 64024
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GnomAD4 exome AF: 0.0000155 AC: 17AN: 1094847Hom.: 2 Cov.: 31 AF XY: 0.0000111 AC XY: 4AN XY: 360747
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GnomAD4 genome ? AF: 0.00000895 AC: 1AN: 111689Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33859
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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 | Invitae | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at