ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.224G>A (p.Gly75Glu)

gnomAD frequency: 0.00004  dbSNP: rs780823805
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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 RCV000472800 SCV000552809 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 75 of the TMEM67 protein (p.Gly75Glu). This variant is present in population databases (rs780823805, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 411582). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 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.
Fulgent Genetics, Fulgent Genetics RCV002475886 SCV002778808 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-11-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525618 SCV003661827 uncertain significance Inborn genetic diseases 2022-11-18 criteria provided, single submitter clinical testing The c.224G>A (p.G75E) alteration is located in exon 2 (coding exon 2) of the TMEM67 gene. This alteration results from a G to A substitution at nucleotide position 224, causing the glycine (G) at amino acid position 75 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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