MCM3AP

minichromosome maintenance complex component 3 associated protein, the group of Transcription and export complex 2|Lysine acetyltransferases

Basic information

Region (hg38): 21:46235133-46286297

Links

ENSG00000160294 ∙ NCBI:8888 ∙ OMIM:603294 ∙ HGNC:6946 ∙ Uniprot:O60318 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (Moderate), mode of inheritance: AR
• peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (Strong), mode of inheritance: AR
• peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	24123876; 28633435; 28969388; 29982295

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM3AP gene.

• not provided (51 variants)
• Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (3 variants)
• Inborn genetic diseases (3 variants)
• MCM3AP-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM3AP 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			3	364	17	384
missense			554	17	11	582
nonsense	15	2	2			19
start loss						0
frameshift	39	3	2			44
inframe indel			8		1	9
splice donor/acceptor (+/-2bp)		13	1			14
splice region		1	15	38	3	57
non coding			7	113	64	184
Total	54	18	577	494	93

Highest pathogenic variant AF is 0.0000591

Variants in MCM3AP

This is a list of pathogenic ClinVar variants found in the MCM3AP region.

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

Position	Type	Phenotype	Significance	ClinVar
21-46235283-G-A			Likely benign (Sep 28, 2023)
21-46235285-C-T			Uncertain significance (Jul 05, 2022)
21-46235292-C-T			Likely benign (Dec 22, 2021)
21-46235293-G-A			Uncertain significance (Jun 13, 2022)
21-46235294-C-G			Uncertain significance (Jul 15, 2022)
21-46235308-T-C			Uncertain significance (Mar 24, 2022)
21-46235332-G-C			Uncertain significance (May 21, 2022)
21-46235336-T-C		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
21-46235338-C-T			Uncertain significance (Apr 28, 2022)
21-46235339-G-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
21-46235349-T-C			Likely benign (Jan 17, 2022)
21-46235361-T-G			Likely benign (Nov 07, 2023)
21-46235363-G-C			Uncertain significance (May 22, 2023)
21-46235365-C-G			Uncertain significance (Dec 21, 2021)
21-46235366-G-A			Uncertain significance (Aug 10, 2022)
21-46235375-G-A			Likely benign (Jan 24, 2023)
21-46235379-C-G			Likely benign (Nov 01, 2023)
21-46235379-C-T			Likely benign (Feb 16, 2023)
21-46235380-G-A		Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development	Uncertain significance (Jul 22, 2024)
21-46235381-T-C			Uncertain significance (Jul 23, 2022)
21-46235381-T-G			Uncertain significance (May 12, 2022)
21-46235383-C-T			Uncertain significance (Aug 30, 2024)
21-46235384-C-G			Uncertain significance (Jul 26, 2022)
21-46235386-G-T			Uncertain significance (Aug 25, 2023)
21-46235388-C-G			Benign/Likely benign (Jan 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM3AP	protein_coding	protein_coding	ENST00000397708	28	51165

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.24e-9	1.00	125633	0	115	125748	0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0407	1129	1.13e+3	0.997	0.0000666	12925
Missense in Polyphen		365	428.62	0.85157		4924
Synonymous	-1.19	505	472	1.07	0.0000304	4028
Loss of Function	5.38	30	82.8	0.362	0.00000405	980

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000597	0.000597
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000272	0.000272
Finnish	0.000325	0.000323
European (Non-Finnish)	0.000594	0.000580
Middle Eastern	0.000272	0.000272
South Asian	0.000535	0.000523
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform GANP: Essential for the generation of high- affinity B-cells against T-cell-dependent antigens by affecting somatic hypermutation at the IgV-regions. May have stimulation- dependent DNA primase activity that would generate extra RNA primers in very rapidely proliferating cells and would support clonal expansion of differentiating B-cells (By similarity). Involved in the nuclear export of poly(A)-containing mRNAs by acting as a scaffold for the TREX-2 complex. The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. {ECO:0000250, ECO:0000269|PubMed:22307388}.

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.685
• rvis_EVS: -2.55
• rvis_percentile_EVS: 0.87

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.756
• ghis: 0.669

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.689

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcm3ap
• 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); hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: mcm3ap
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: immune system process;mRNA export from nucleus;protein transport;poly(A)+ mRNA export from nucleus;mRNA transport
• Cellular component: nucleus;nuclear pore;nucleoplasm;cytoplasm;cytosol;nuclear membrane;transcription export complex 2
• Molecular function: nucleic acid binding;transferase activity, transferring acyl groups