ClinVar Miner

Submissions for variant NM_182916.3(TRNT1):c.1057-7C>G (rs368078167)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497594 SCV000589686 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing The c.1057-7 C>G variant has been published in three unrelated patients with congential sideroblastic anemia who also harbored the same missense variant in the TRNT1 gene; the phase of the two variants was not reported (Chakraborty et al. 2014). The c.1057-7 C>G variant is observed in 13/66240 (0.02%) alleles from individuals of European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is not conserved. In-silico splice prediction models were not informative as to whether or not c.1057-7 C>G is expected to affect normal gene splicing, and in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000144948 SCV000958025 uncertain significance Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay 2019-12-24 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the TRNT1 gene. It does not directly change the encoded amino acid sequence of the TRNT1 protein. This variant is present in population databases (rs368078167, ExAC 0.02%). This variant has been observed in several individuals affected with sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) (PMID: 25193871). ClinVar contains an entry for this variant (Variation ID: 157615). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV001249657 SCV001423621 likely pathogenic Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay; Retinitis pigmentosa and erythrocytic microcytosis 2018-10-31 criteria provided, single submitter clinical testing [ACMG/AMP: PM2, PM3, PP3, PP5] This alteration is absent from or rarely observed in large-scale population databases [PM2], is detected in trans with a known pathogenic variant [PM3], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].
OMIM RCV000144948 SCV000191964 pathogenic Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay 2014-10-30 no assertion criteria provided literature only

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