ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.873G>A (p.Ala291=)

gnomAD frequency: 0.00004  dbSNP: rs138794621
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153466 SCV000202973 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000533988 SCV000656963 uncertain significance 3-methylcrotonyl-CoA carboxylase 1 deficiency 2022-07-14 criteria provided, single submitter clinical testing This sequence change affects codon 291 of the MCCC1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MCCC1 protein. This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. This variant is present in population databases (rs138794621, gnomAD 0.02%). This variant has been observed in individual(s) with MCCC1-related conditions (PMID: 30626930). ClinVar contains an entry for this variant (Variation ID: 167271). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Ambry Genetics RCV002514957 SCV003564146 uncertain significance Inborn genetic diseases 2021-06-03 criteria provided, single submitter clinical testing The c.873G>A (p.A291A) alteration is located in exon 8 (coding exon 8) of the MCCC1 gene. This alteration consists of a G to A substitution at nucleotide position 873. This nucleotide substitution does not change the alanine at codon 291. However, this change occurs in the last base pair of coding exon 8, which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275511 SCV001460696 uncertain significance Methylcrotonyl-CoA carboxylase deficiency 2020-09-16 no assertion criteria provided clinical testing

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