ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.1037-3C>G

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003037427 SCV003441028 pathogenic not provided 2024-09-30 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the TYR gene. It does not directly change the encoded amino acid sequence of the TYR protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs779929859, gnomAD 0.01%). This variant has been observed in individual(s) with clinical features of autosomal recessive TYR-related conditions (PMID: 27734839; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2137234). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Fulgent Genetics, Fulgent Genetics RCV005010893 SCV005631368 likely pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2024-06-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004536545 SCV004117051 likely pathogenic TYR-related disorder 2023-12-30 no assertion criteria provided clinical testing The TYR c.1037-3C>G variant is predicted to interfere with splicing. This variant is predicted to both decrease the strength of the canonical splice site and introduce a cryptic splice site based on available splicing prediction software (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). This variant has been reported along with a second TYR variant in at least two individuals with oculocutaneous albinism (Mauri et al. 2017. PubMed ID: 27734839). This variant is reported in 0.010% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Given the evidence, we interpret this variant as likely pathogenic.

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