ClinVar Miner

Submissions for variant NM_000550.3(TYRP1):c.415G>A (p.Glu139Lys)

gnomAD frequency: 0.00006  dbSNP: rs201789348
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000313512 SCV000333135 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000313512 SCV002135299 likely pathogenic not provided 2023-09-27 criteria provided, single submitter clinical testing 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TYRP1 protein function. ClinVar contains an entry for this variant (Variation ID: 282003). This missense change has been observed in individual(s) with clinical features of ocular albinism (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs201789348, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 139 of the TYRP1 protein (p.Glu139Lys).
Molecular Genetics, University Hospital Bordeaux RCV004797801 SCV005049514 pathogenic Oculocutaneous albinism type 3 2023-06-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701367 SCV005204207 uncertain significance not specified 2024-06-20 criteria provided, single submitter clinical testing Variant summary: TYRP1 c.415G>A (p.Glu139Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250898 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.415G>A in individuals affected with Oculocutaneous albinism type 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 282003). Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV005049512 SCV005677700 likely pathogenic Oculocutaneous albinism type 3; MELANESIAN BLOND HAIR 2024-06-22 criteria provided, single submitter clinical testing

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