Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002281812 | SCV002572278 | likely benign | not specified | 2022-08-23 | criteria provided, single submitter | clinical testing | Variant summary: SLC4A11 c.1723G>A (p.Val575Met) results in a conservative amino acid change located in the Bicarbonate transporter-like, transmembrane domain (IPR011531) of the encoded protein sequence. It lies at the N terminus of TM6, where it makes the closest contact of any residue in the dimer interface, and it may also impact the positioning of extracellular loop 3 (Badior_2016). Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 279758 control chromosomes, predominantly at a frequency of 0.0018 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately two fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC4A11 causing Corneal Dystrophy And Perceptive Deafness phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1723G>A has been reported in the literature in at least one individual affected with Fuchs corneal dystrophy (Riazuddin_2010). The report does not provide unequivocal conclusions about association of the variant with Corneal Dystrophy And Perceptive Deafness. Functional studies report this variant processed similar to the WT on immunoblot analyses but exhibited partial loss of localization at the membrane (Riazuddin_2010, Malhotra_2020). However, another functional study showed this variant results in no effect on cell surface abundance and cell surface SLC4A11 localization (Alka_2018). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. |
| Labcorp Genetics |
RCV003101626 | SCV003292570 | likely benign | not provided | 2024-03-02 | criteria provided, single submitter | clinical testing |