rs201225704
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000052.7(ATP7A):āc.3449T>Cā(p.Ile1150Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,209,407 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., 6 hem., cov: 23)
Exomes š: 0.000041 ( 0 hom. 13 hem. )
Consequence
ATP7A
NM_000052.7 missense
NM_000052.7 missense
Scores
2
7
8
Clinical Significance
Conservation
PhyloP100: 5.63
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17810392).
BP6
Variant X-78033759-T-C is Benign according to our data. Variant chrX-78033759-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 210452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.3449T>C | p.Ile1150Thr | missense_variant | 17/23 | ENST00000341514.11 | NP_000043.4 | |
ATP7A | NM_001282224.2 | c.3215T>C | p.Ile1072Thr | missense_variant | 16/22 | NP_001269153.1 | ||
ATP7A | NR_104109.2 | n.622T>C | non_coding_transcript_exon_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.3449T>C | p.Ile1150Thr | missense_variant | 17/23 | 1 | NM_000052.7 | ENSP00000345728.6 |
Frequencies
GnomAD3 genomes AF: 0.000161 AC: 18AN: 111950Hom.: 0 Cov.: 23 AF XY: 0.000176 AC XY: 6AN XY: 34114
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GnomAD3 exomes AF: 0.0000873 AC: 16AN: 183317Hom.: 0 AF XY: 0.0000885 AC XY: 6AN XY: 67811
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GnomAD4 exome AF: 0.0000410 AC: 45AN: 1097405Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 13AN XY: 362875
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GnomAD4 genome AF: 0.000161 AC: 18AN: 112002Hom.: 0 Cov.: 23 AF XY: 0.000176 AC XY: 6AN XY: 34176
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | ATP7A: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
ATP7A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 23, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0050
.;B
Vest4
MVP
MPC
0.29
ClinPred
T
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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