ClinVar Miner

Submissions for variant NM_003611.3(OFD1):c.3G>A (p.Met1Ile)

gnomAD frequency: 0.00002  dbSNP: rs778840618
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001333140 SCV001525636 uncertain significance Joubert syndrome 10 2018-04-02 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001859306 SCV002178464 uncertain significance Familial aplasia of the vermis; Orofaciodigital syndrome I 2025-01-05 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the OFD1 mRNA. The next in-frame methionine is located at codon 2. This variant is present in population databases (rs778840618, gnomAD 0.02%). Disruption of the initiator codon has been observed in individual(s) with clinical features of X-linked recessive primary ciliary dyskinesia (PMID: 35728977). ClinVar contains an entry for this variant (Variation ID: 1031340). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics RCV004035756 SCV002619595 uncertain significance Primary ciliary dyskinesia 2018-07-24 criteria provided, single submitter clinical testing The p.M1? variant (also known as c.3G>A), located in coding exon 1 of the OFD1 gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon (ATG). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. However, there are in-frame methionines at amino acid positions 2 and 7 that could be used as an alternate initiation codon, and the significance of the N-terminus for this protein is not well established. In addition, this amino acid position is conserved only in primates. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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