rs115985012
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_022089.4(ATP13A2):c.3342C>T(p.Thr1114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,612,672 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 20 hom. )
Consequence
ATP13A2
NM_022089.4 synonymous
NM_022089.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.800
Genes affected
ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]
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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 (BayesDel_noAF=-0.71).
BP6
?
Variant 1-16986526-G-A is Benign according to our data. Variant chr1-16986526-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 588527.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=3}. Variant chr1-16986526-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.8 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00221 (337/152246) while in subpopulation NFE AF= 0.00407 (277/67996). AF 95% confidence interval is 0.00368. There are 0 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP13A2 | NM_022089.4 | c.3342C>T | p.Thr1114= | synonymous_variant | 28/29 | ENST00000326735.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP13A2 | ENST00000326735.13 | c.3342C>T | p.Thr1114= | synonymous_variant | 28/29 | 1 | NM_022089.4 | A1 | |
ENST00000446261.1 | n.187+7414G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00222 AC: 337AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00231 AC: 567AN: 245592Hom.: 2 AF XY: 0.00245 AC XY: 326AN XY: 133216
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GnomAD4 exome AF: 0.00351 AC: 5124AN: 1460426Hom.: 20 Cov.: 68 AF XY: 0.00341 AC XY: 2476AN XY: 726548
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GnomAD4 genome ? AF: 0.00221 AC: 337AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.00202 AC XY: 150AN XY: 74424
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | ATP13A2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 06, 2020 | - - |
Kufor-Rakeb syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2016 | 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. - |
Computational scores
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Name
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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