ClinVar Miner

Submissions for variant NM_145691.4(ATPAF2):c.133+1G>T

gnomAD frequency: 0.00004  dbSNP: rs147941728
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485392 SCV000571789 pathogenic not provided 2023-11-20 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 34440436, 34930662)
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000851186 SCV000993429 uncertain significance Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 2019-04-06 criteria provided, single submitter research ACMG codes: PM2
3billion RCV000851186 SCV002521249 pathogenic Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The patient's phenotype is considered compatible with ATPAF2 related disorder (3billion dataset). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV000485392 SCV003295206 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the ATPAF2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ATPAF2 cause disease. This variant is present in population databases (rs147941728, gnomAD 0.03%). Disruption of this splice site has been observed in individual(s) with ATPAF2-related conditions (PMID: 34440436). ClinVar contains an entry for this variant (Variation ID: 422342). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000851186 SCV003807784 uncertain significance Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 2022-11-25 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 supporting

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