NM_001253852.3(AP4B1):c.664del (p.Leu222fs) AND Hereditary spastic paraplegia 47

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Mar 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001775007.7

Allele description [Variation Report for NM_001253852.3(AP4B1):c.664del (p.Leu222fs)]

NM_001253852.3(AP4B1):c.664del (p.Leu222fs)

Genes:

AP4B1-AS1:AP4B1 antisense RNA 1 [Gene - HGNC]
AP4B1:adaptor related protein complex 4 subunit beta 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_001253852.3(AP4B1):c.664del (p.Leu222fs)

Other names:

p.Leu222CysfsTer31

HGVS:

NC_000001.11:g.113900354del
NG_031901.1:g.9766del
NG_057565.1:g.736del
NM_001253852.3:c.664delMANE SELECT
NM_001253853.3:c.367del
NM_001308312.2:c.160del
NM_006594.5:c.664del
NP_001240781.1:p.Leu222fs
NP_001240782.1:p.Leu123fs
NP_001295241.1:p.Leu54fs
NP_006585.2:p.Leu222fs
LRG_1219:g.736del
NC_000001.10:g.114442976del
NM_001253852.1:c.664delC
NM_001253852.2:c.664del
NM_006594.3:c.664del
NM_006594.3:c.664delC
NR_037864.1:n.851del
NR_125965.1:n.1019del

Protein change:

L123fs

Links:

OMIM: 607245.0002; dbSNP: rs1571563769

NCBI 1000 Genomes Browser:

rs1571563769

Molecular consequence:

NM_001253852.3:c.664del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001253853.3:c.367del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001308312.2:c.160del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006594.5:c.664del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_037864.1:n.851del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_125965.1:n.1019del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Hereditary spastic paraplegia 47
Synonyms:: Cerebral palsy, spastic quadriplegic, 5; adaptor protein 4 (AP-4) deficiency syndrome; Spastic paraplegia 47, autosomal recessive
Identifiers:: MONDO: MONDO:0013551; MedGen: C3279738; Orphanet: 280763; OMIM: 614066

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044931	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002004103	Novin Medical Genetic Laboratory	no assertion criteria provided	Pathogenic (Feb 2, 2019)	germline	clinical testing
SCV004236950	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 16, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004806266	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005088735	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2020)	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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Persian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) .

Bauer P, Leshinsky-Silver E, Blumkin L, Schlipf N, Schröder C, Schicks J, Lev D, Riess O, Lerman-Sagie T, Schöls L.

Neurogenetics. 2012 Feb;13(1):73-6. doi: 10.1007/s10048-012-0314-0.

PubMed [citation]

PMID:: 22290197

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, SCV000044931.3

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

Description

In 2 sibs, born of consanguineous Arab parents, with autosomal recessive complicated spastic paraplegia-47 (SPG47; 614066), Bauer et al. (2012) identified a homozygous 1-bp deletion (664delC) in exon 5 of the AP4B1 gene, resulting in a frameshift and premature termination. Each unaffected parent was heterozygous for the mutation, which was not found in 316 Caucasian and 200 ethnically matched control chromosomes.

#	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 Novin Medical Genetic Laboratory, SCV002004103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Persian	1	not provided	not provided	clinical testing	not provided

Description

A homozygous mutation p.L54Cfs*30 detected in a 9 year-old Iranian girl with initial diagnosis as Cerebral Palsy. Symptoms is as following: microcephaly, mental retardation, seizure, speech problems and muscle spasm.

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

From Revvity Omics, Revvity, SCV004236950.1

#	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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004806266.1

#	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

From Breakthrough Genomics, Breakthrough Genomics, SCV005088735.2

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

Description

This variant has been previously reported in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis, intellectual disability, seizures, periventricular white matter changes and thin corpus callosum in homozygous state and absent in controls studied [PMID: 22290197].

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine