NM_003906.5(MCM3AP):c.3476_3477del (p.Gln1159fs) AND Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 29, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002251773.2

Allele description

NM_003906.5(MCM3AP):c.3476_3477del (p.Gln1159fs)

Gene:

MCM3AP:minichromosome maintenance complex component 3 associated protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_003906.5(MCM3AP):c.3476_3477del (p.Gln1159fs)

HGVS:

NC_000021.9:g.46260897_46260898del
NG_033881.1:g.29425_29426del
NM_003906.5:c.3476_3477delMANE SELECT
NP_003897.2:p.Gln1159fs
NC_000021.8:g.47680811_47680812del
NM_003906.3:c.3476_3477delAA
NM_003906.4:c.3476_3477delAA

Protein change:

Q1159fs

Links:

OMIM: 603294.0009; dbSNP: rs756431692

NCBI 1000 Genomes Browser:

rs756431692

Molecular consequence:

NM_003906.5:c.3476_3477del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development
Identifiers:: MONDO: MONDO:0029131; MedGen: C4748283; OMIM: 618124

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002520452	OMIM	no assertion criteria provided	Pathogenic (Apr 21, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004807542	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520452

OMIM

no assertion criteria provided

Pathogenic
(Apr 21, 2022)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004807542

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 29, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content.

Woldegebriel R, Kvist J, Andersson N, Õunap K, Reinson K, Wojcik MH, Bijlsma EK, Hoffer MJV, Ryan MM, Stark Z, Walsh M, Cuppen I, van den Boogaard MH, Bharucha-Goebel D, Donkervoort S, Winchester S, Zori R, Bönnemann CG, Maroofian R, O'Connor E, Houlden H, Zhao F, et al.

Hum Mol Genet. 2020 Jun 3;29(9):1426-1439. doi: 10.1093/hmg/ddaa051.

PubMed [citation]

PMID:: 32202298
PMCID:: PMC7297229

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV002520452.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient (NL2) of Dutch and Thai ancestry with autosomal recessive peripheral neuropathy with impaired intellectual development (PNRIID; 618124), Woldegebriel et al. (2020) identified compound heterozygous mutations in the MCM3AP gene: a paternally inherited 2-bp deletion (c.3476_3477del), predicted to result in a frameshift and premature termination (Gln1159ArgfsTer8), and a maternally inherited c.4290+3G-T transversion (603294.0010), predicted to result in abnormal splicing. The mutations, which were found by whole-exome sequencing, were not present in the ExAC database. MCM3AP mRNA expression was reduced in patient fibroblasts compared to controls, and GANP protein levels were reduced at the level of the nuclear envelope in patient fibroblasts compared to controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004807542.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 19, 2024

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