ClinVar Miner

Submissions for variant NM_003052.5(SLC34A1):c.644+1G>A

gnomAD frequency: 0.00004  dbSNP: rs201304511
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001387314 SCV001587914 pathogenic not provided 2023-11-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the SLC34A1 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), and loss-of-function variants in SLC34A1 are known to be pathogenic (PMID: 26047794). This variant is present in population databases (rs201304511, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of infantile hypercalcemia (PMID: 26047794, 28893421, 29959532). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 234926). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003929923 SCV004738986 pathogenic SLC34A1-related condition 2024-02-15 criteria provided, single submitter clinical testing The SLC34A1 c.644+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in the homozygous and compound heterozygous states in individuals with infantile hypercalcemia (Schlingmann et al 2016. PubMed ID: 26047794; Daga et al 2017. PubMed ID: 28893421; Hureaux et al 2018. PubMed ID: 29959532). This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Variants that disrupt consensus splice donor sites in SLC34A1 are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000223675 SCV000280015 pathogenic Hypercalcemia, infantile, 2 2016-10-06 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV000662327 SCV000784659 likely pathogenic Nephrocalcinosis; Nephrolithiasis 2017-09-08 no assertion criteria provided literature only

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