NM_004722.4(AP4M1):c.861dup (p.Asp288fs) AND Hereditary spastic paraplegia 50

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2023
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:: RCV003506953.2

Allele description [Variation Report for NM_004722.4(AP4M1):c.861dup (p.Asp288fs)]

NM_004722.4(AP4M1):c.861dup (p.Asp288fs)

Gene:

AP4M1:adaptor related protein complex 4 subunit mu 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_004722.4(AP4M1):c.861dup (p.Asp288fs)

HGVS:

NC_000007.14:g.100105471dup
NG_016312.1:g.8965dup
NG_029454.1:g.19389dup
NG_029454.2:g.26701dup
NM_001363671.2:c.882dup
NM_004722.4:c.861dupMANE SELECT
NP_001350600.1:p.Asp295fs
NP_004713.2:p.Asp288fs
NC_000007.13:g.99703092_99703093insC
NC_000007.13:g.99703094dup

Protein change:

D288fs

Molecular consequence:

NM_001363671.2:c.882dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004722.4:c.861dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary spastic paraplegia 50 (SPG50)
Synonyms:: Spastic paraplegia 50, autosomal recessive
Identifiers:: MONDO: MONDO:0013048; MedGen: C2752008; Orphanet: 280763; OMIM: 612936

Recent activity

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von Willebrand factor, partial [Octodon degus]
von Willebrand factor, partial [Octodon degus]
gi|2020334544|gb|QTI96926.1|

Protein
Sargassum elegans voucher GENT-ODC1303 cytochrome oxidase subunit 3 (cox3) gene,...
Sargassum elegans voucher GENT-ODC1303 cytochrome oxidase subunit 3 (cox3) gene, partial cds; mitochondrial
gi|855198580|gb|KP720476.1|

Nucleotide
tep-1 TEP (ThiolEster containing Protein) [Caenorhabditis elegans]
tep-1 TEP (ThiolEster containing Protein) [Caenorhabditis elegans]
Gene ID:173367

Gene
F48D6.4 28S ribosomal protein S36, mitochondrial;39S ribosomal protein L52, mito...
F48D6.4 28S ribosomal protein S36, mitochondrial;39S ribosomal protein L52, mitochondrial;NADH-ubiquinone oxidoreductase subunit [Caenorhabditis elegans]
Gene ID:180697

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004311031	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24700674, 25496299, 25558065, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004311031

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 1, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Citations

PubMed

Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features.

Tüysüz B, Bilguvar K, Koçer N, Yalçınkaya C, Çağlayan O, Gül E, Sahin S, Çomu S, Günel M.

Am J Med Genet A. 2014 Jul;164A(7):1677-85. doi: 10.1002/ajmg.a.36514. Epub 2014 Apr 3.

PubMed [citation]

PMID:: 24700674

A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency.

Jameel M, Klar J, Tariq M, Moawia A, Altaf Malik N, Seema Waseem S, Abdullah U, Naeem Khan T, Raininko R, Baig SM, Dahl N.

BMC Med Genet. 2014 Dec 14;15:133. doi: 10.1186/s12881-014-0133-2.

PubMed [citation]

PMID:: 25496299
PMCID:: PMC4292821

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004311031.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AP4M1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp288Argfs*2) in the AP4M1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AP4M1 are known to be pathogenic (PMID: 24700674, 25496299, 25558065).

#	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: Sep 29, 2024

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