ClinVar Miner

Submissions for variant NM_001142966.3(GREB1L):c.683C>T (p.Ser228Phe)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV003994669 SCV004812557 uncertain significance Hearing loss, autosomal dominant 80 2024-02-05 criteria provided, single submitter clinical testing This sequence change in GREB1L is predicted to replace serine with phenylalanine at codon 228, p.(Ser228Phe). The serine residue is moderately conserved (100 vertebrates, Multiz Alignments), and is located in a region of the GREB1 N-terminal domain that is highly intolerant to missense variation (amino acids 227-229). There is a large physicochemical difference between serine and phenylalanine. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.0002% (2/1,078,756 alleles) in the European (non-Finnish) population, which is consistent with autosomal dominant deafness. To our knowledge, this variant has not been previously reported in the relevant scientific literature or databases. Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.147). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM1, PM2_Supporting, BP4.

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