rs181665434
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000052.7(ATP7A):c.3801+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,206,679 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 325 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00050 ( 0 hom., 11 hem., cov: 22)
Exomes 𝑓: 0.00080 ( 0 hom. 314 hem. )
Consequence
ATP7A
NM_000052.7 splice_donor_region, intron
NM_000052.7 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.2049
2
Clinical Significance
Conservation
PhyloP100: 0.967
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant X-78040739-T-C is Benign according to our data. Variant chrX-78040739-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 465120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Hemizygotes in GnomAd4 at 11 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.3801+6T>C | splice_donor_region_variant, intron_variant | ENST00000341514.11 | |||
ATP7A | NM_001282224.2 | c.3567+6T>C | splice_donor_region_variant, intron_variant | ||||
ATP7A | NR_104109.2 | n.974+6T>C | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.3801+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_000052.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000500 AC: 56AN: 111969Hom.: 0 Cov.: 22 AF XY: 0.000323 AC XY: 11AN XY: 34105
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GnomAD3 exomes AF: 0.000502 AC: 92AN: 183384Hom.: 0 AF XY: 0.000663 AC XY: 45AN XY: 67870
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GnomAD4 exome AF: 0.000804 AC: 880AN: 1094656Hom.: 0 Cov.: 30 AF XY: 0.000872 AC XY: 314AN XY: 360210
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GnomAD4 genome ? AF: 0.000500 AC: 56AN: 112023Hom.: 0 Cov.: 22 AF XY: 0.000322 AC XY: 11AN XY: 34169
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2019 | This alteration is classified as 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. - |
Ehlers-Danlos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 01, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2020 | - - |
Menkes kinky-hair syndrome;C0268353:Cutis laxa, X-linked;C1845359:X-linked distal spinal muscular atrophy type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at