rs760621295
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006739.4(MCM5):c.850_851del(p.Arg284GlyfsTer49) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000889 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
MCM5
NM_006739.4 frameshift
NM_006739.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.85
Genes affected
MCM5 (HGNC:6948): (minichromosome maintenance complex component 5) The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCM5 | NM_006739.4 | c.850_851del | p.Arg284GlyfsTer49 | frameshift_variant | 7/17 | ENST00000216122.9 | |
MCM5 | XM_006724242.5 | c.850_851del | p.Arg284GlyfsTer49 | frameshift_variant | 7/18 | ||
MCM5 | XM_047441366.1 | c.850_851del | p.Arg284GlyfsTer49 | frameshift_variant | 7/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCM5 | ENST00000216122.9 | c.850_851del | p.Arg284GlyfsTer49 | frameshift_variant | 7/17 | 1 | NM_006739.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251424Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461650Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727084
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Meier-Gorlin syndrome 8 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 10, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change creates a premature translational stop signal (p.Arg284Glyfs*49) in the MCM5 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MCM5 cause disease. This variant is present in population databases (rs760621295, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Meier-Gorlin syndrome (PMID: 28198391). ClinVar contains an entry for this variant (Variation ID: 430636). 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. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at