MCM10

minichromosome maintenance 10 replication initiation factor

Basic information

Region (hg38): 10:13161558-13211110

Links

ENSG00000065328 ∙ NCBI:55388 ∙ OMIM:609357 ∙ HGNC:18043 ∙ Uniprot:Q7L590 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 80 with or without congenital cardiomyopathy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 80 with or without congenital cardiomyopathy	AR	Allergy/Immunology/Infectious; Cardiovascular	Individuals are susceptible to severe infections, and early and aggressive management may be beneficial related to morbidity and mortality; BMT has been described; Individuals have been described with cardiomyopathy, and early diagnosis may allow management	Allergy/Immunology/Infectious; Cardiovascular	32865517; 33712616

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM10 gene.

• Immunodeficiency 80 with or without congenital cardiomyopathy (2 variants)
• Fetal Cardiomyopathy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	4	8
missense			38	7	3	48
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1			2	1	4
non coding					11	11
Total	1	0	38	11	18

Highest pathogenic variant AF is 0.00000657

Variants in MCM10

This is a list of pathogenic ClinVar variants found in the MCM10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-13164233-A-T		not specified	Benign (Jan 24, 2024)
10-13170884-C-T		not specified	Benign (Jan 24, 2024)
10-13170915-C-A			Benign (Apr 10, 2018)
10-13170981-G-A		not specified	Uncertain significance (May 05, 2023)
10-13171015-G-A		not specified	Likely benign (Jul 14, 2023)
10-13171022-T-C			Likely benign (Aug 01, 2024)
10-13171088-G-C		not specified	Uncertain significance (Jun 29, 2023)
10-13171119-G-A		not specified	Uncertain significance (Aug 14, 2023)
10-13171148-TG-T		Immunodeficiency 80 with or without congenital cardiomyopathy • Fetal Cardiomyopathy	Pathogenic (Mar 23, 2023)
10-13171200-A-G		not specified	Likely benign (Jan 16, 2024)
10-13171215-C-T		not specified	Uncertain significance (Aug 04, 2023)
10-13171227-G-A		not specified	Uncertain significance (Nov 21, 2023)
10-13171243-A-G		not specified	Uncertain significance (Nov 07, 2023)
10-13171247-G-A		not specified	Likely benign (Aug 01, 2024)
10-13172436-C-T		not specified	Uncertain significance (Apr 07, 2022)
10-13172640-G-A		not specified	Uncertain significance (Jun 28, 2023)
10-13172762-C-G		not specified	Likely benign (Apr 08, 2024)
10-13172812-A-G		not specified	Benign (Jan 24, 2024)
10-13175515-A-G		not specified	Uncertain significance (Aug 01, 2022)
10-13175587-G-T		not specified	Uncertain significance (Jun 23, 2021)
10-13175592-A-G		not specified	Likely benign (Aug 28, 2023)
10-13175623-A-G		not specified	Uncertain significance (Sep 14, 2022)
10-13175630-G-A		not specified	Uncertain significance (Apr 08, 2024)
10-13175636-C-T			Likely benign (Apr 01, 2022)
10-13175652-T-G		not specified	Uncertain significance (Dec 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM10	protein_coding	protein_coding	ENST00000484800	19	49551

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.38e-15	0.977	125679	0	69	125748	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.167	496	486	1.02	0.0000280	5674
Missense in Polyphen		150	138.79	1.0808		1657
Synonymous	0.731	171	184	0.931	0.0000111	1672
Loss of Function	2.48	31	49.9	0.621	0.00000269	602

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000695	0.000693
Ashkenazi Jewish	0.00	0.00
East Asian	0.000550	0.000544
Finnish	0.000326	0.000323
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000550	0.000544
South Asian	0.000262	0.000261
Other	0.000337	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Additionally, plays a role in preventing DNA damage during replication. Key effector of the RBBP6 and ZBTB38-mediated regulation of DNA-replication and common fragile sites stability; acts as a direct target of transcriptional repression by ZBTB38 (PubMed:24726359). {ECO:0000269|PubMed:11095689, ECO:0000269|PubMed:15136575, ECO:0000269|PubMed:17699597, ECO:0000269|PubMed:19608746, ECO:0000269|PubMed:24726359}.
• Pathway: Cell Cycle;DNA Replication;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA Replication;G1/S Transition;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.937
• rvis_EVS: -0.03
• rvis_percentile_EVS: 50.54

Haploinsufficiency Scores

• pHI: 0.264
• hipred: N
• hipred_score: 0.277
• ghis: 0.636

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.648

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mcm10
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA replication initiation;cellular response to DNA damage stimulus;cell population proliferation
• Cellular component: nucleus;nucleoplasm;nucleolus;replication fork protection complex
• Molecular function: DNA replication origin binding;double-stranded DNA binding;single-stranded DNA binding;protein binding;enzyme binding;identical protein binding;metal ion binding