NM_001253852.3(AP4B1):c.616C>T (p.Arg206Ter) AND Hereditary spastic paraplegia 47

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 24, 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:: RCV002539788.2

Allele description [Variation Report for NM_001253852.3(AP4B1):c.616C>T (p.Arg206Ter)]

NM_001253852.3(AP4B1):c.616C>T (p.Arg206Ter)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_001253852.3(AP4B1):c.616C>T (p.Arg206Ter)

HGVS:

NC_000001.11:g.113901237G>A
NG_031901.1:g.8883C>T
NG_057565.1:g.1619G>A
NM_001253852.3:c.616C>TMANE SELECT
NM_001253853.3:c.319C>T
NM_001308312.2:c.114-837C>T
NM_006594.5:c.616C>T
NP_001240781.1:p.Arg206Ter
NP_001240782.1:p.Arg107Ter
NP_006585.2:p.Arg206Ter
LRG_1219:g.1619G>A
NC_000001.10:g.114443859G>A
NR_037864.1:n.1734G>A
NR_125965.1:n.1902G>A

Protein change:

R107*

Links:

dbSNP: rs762612591

NCBI 1000 Genomes Browser:

rs762612591

Molecular consequence:

NM_001308312.2:c.114-837C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_037864.1:n.1734G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_125965.1:n.1902G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001253852.3:c.616C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001253853.3:c.319C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_006594.5:c.616C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003034100	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22290197, 24700674, 24781758, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003034100

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 24, 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

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

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

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003034100.2

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

Description

This sequence change creates a premature translational stop signal (p.Arg206*) in the AP4B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AP4B1 are known to be pathogenic (PMID: 22290197, 24700674, 24781758). This variant is present in population databases (rs762612591, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1299776). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2024

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