1-1516000-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001170535.3(ATAD3A):c.206-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,412 control chromosomes in the GnomAD database, including 52,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.35 ( 14797 hom., cov: 32)
Exomes 𝑓: 0.18 ( 37240 hom. )
Consequence
ATAD3A
NM_001170535.3 splice_polypyrimidine_tract, intron
NM_001170535.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00006045
2
Clinical Significance
Conservation
PhyloP100: -4.17
Genes affected
ATAD3A (HGNC:25567): (ATPase family AAA domain containing 3A) This gene encodes a ubiquitously expressed mitochondrial membrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. This gene is a member of the ATPase family AAA-domain containing 3 gene family which, in humans, includes two other paralogs. Naturally occurring mutations in this gene are associated with distinct neurological syndromes including Harel-Yoon syndrome. High-level expression of this gene is associated with poor survival in breast cancer patients. A homozygous knockout of the orthologous gene in mice results in embryonic lethality at day 7.5 due to growth retardation and defective development of the trophoblast lineage. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 1-1516000-T-C is Benign according to our data. Variant chr1-1516000-T-C is described in ClinVar as [Benign]. Clinvar id is 1185402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATAD3A | NM_001170535.3 | c.206-12T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000378756.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATAD3A | ENST00000378756.8 | c.206-12T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001170535.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.353 AC: 53633AN: 152042Hom.: 14744 Cov.: 32
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GnomAD3 exomes AF: 0.276 AC: 69034AN: 250102Hom.: 13771 AF XY: 0.261 AC XY: 35299AN XY: 135396
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GnomAD4 exome AF: 0.185 AC: 270122AN: 1461252Hom.: 37240 Cov.: 33 AF XY: 0.187 AC XY: 136263AN XY: 726938
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GnomAD4 genome AF: 0.353 AC: 53748AN: 152160Hom.: 14797 Cov.: 32 AF XY: 0.359 AC XY: 26693AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. - |
Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Harel-Yoon syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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Name
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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