ENST00000518221.5:c.-15+352G>A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000518221.5(MCM4):c.-15+352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Consequence
MCM4
ENST00000518221.5 intron
ENST00000518221.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.61
Genes affected
MCM4 (HGNC:6947): (minichromosome maintenance complex component 4) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MCM4 | ENST00000518221.5 | c.-15+352G>A | intron_variant | Intron 1 of 4 | 4 | ENSP00000430329.1 | ||||
| MCM4 | ENST00000649838.1 | c.-357G>A | upstream_gene_variant | ENSP00000497648.1 | ||||||
| MCM4 | ENST00000649919.1 | c.-423G>A | upstream_gene_variant | ENSP00000498202.1 | ||||||
| MCM4 | ENST00000648407.1 | c.-357G>A | upstream_gene_variant | ENSP00000497881.1 |
Frequencies
GnomAD3 genomes 0.000125 AC: 19AN: 152242Hom.: 0 Cov.: 32
GnomAD3 genomes
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152242
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.000125 AC: 19AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74390
GnomAD4 genome
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32
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AN XY:
74390
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at