NM_001253852.3(AP4B1):c.337A>G (p.Arg113Gly) AND Hereditary spastic paraplegia 47

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 2019
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:: RCV001065696.2

Allele description [Variation Report for NM_001253852.3(AP4B1):c.337A>G (p.Arg113Gly)]

NM_001253852.3(AP4B1):c.337A>G (p.Arg113Gly)

Gene:

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.337A>G (p.Arg113Gly)

HGVS:

NC_000001.11:g.113902639T>C
NG_031901.1:g.7481A>G
NG_057565.1:g.3021T>C
NM_001253852.3:c.337A>GMANE SELECT
NM_001253853.3:c.40A>G
NM_001308312.2:c.113+1966A>G
NM_006594.5:c.337A>G
NP_001240781.1:p.Arg113Gly
NP_001240782.1:p.Arg14Gly
NP_006585.2:p.Arg113Gly
LRG_1219:g.3021T>C
NC_000001.10:g.114445261T>C
NM_006594.3:c.337A>G

Protein change:

R113G

Links:

dbSNP: rs1668423302

NCBI 1000 Genomes Browser:

rs1668423302

Molecular consequence:

NM_001308312.2:c.113+1966A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001253852.3:c.337A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001253853.3:c.40A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006594.5:c.337A>G - missense variant - [Sequence Ontology: SO:0001583]

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

carbohydrate-binding protein [Enterococcus mundtii]
carbohydrate-binding protein [Enterococcus mundtii]
gi|1297866956|gnl|PRJNA353761|EM483 90|gb|AUB54247.1|

Protein
Alg11 [Arvicanthis niloticus]
Alg11 [Arvicanthis niloticus]
Gene ID:117721717

Gene
Stt3a [Arvicanthis niloticus]
Stt3a [Arvicanthis niloticus]
Gene ID:117699123

Gene
PLCB4 [Strigops habroptila]
PLCB4 [Strigops habroptila]
Gene ID:115609999

Gene

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
SCV001230668	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2019)	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

SCV001230668

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2019)

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001230668.1

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

Description

This sequence change replaces arginine with glycine at codon 113 of the AP4B1 protein (p.Arg113Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with AP4B1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine