chrX-78029271-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000052.7(ATP7A):c.2938C>T(p.Arg980Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R980R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000052.7 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP7A | NM_000052.7 | c.2938C>T | p.Arg980Ter | stop_gained | 15/23 | ENST00000341514.11 | |
ATP7A | NM_001282224.2 | c.2704C>T | p.Arg902Ter | stop_gained | 14/22 | ||
ATP7A | NR_104109.2 | n.285-2129C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP7A | ENST00000341514.11 | c.2938C>T | p.Arg980Ter | stop_gained | 15/23 | 1 | NM_000052.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Menkes kinky-hair syndrome Pathogenic:2Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 1998 | - - |
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium Ii, University Of Miami | Jan 06, 2016 | - - |
Menkes kinky-hair syndrome;C0268353:Cutis laxa, X-linked;C1845359:X-linked distal spinal muscular atrophy type 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2020 | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Menkes disease (PMID: 11241493). This variant is also known as 3083C>T. ClinVar contains an entry for this variant (Variation ID: 11784). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg980*) in the ATP7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7A are known to be pathogenic (PMID: 11241493, 20652413). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at