NM_001253852.3(AP4B1):c.319C>T (p.Arg107Trp) AND Hereditary spastic paraplegia 47

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Feb 2, 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:: RCV001028105.6

Allele description [Variation Report for NM_001253852.3(AP4B1):c.319C>T (p.Arg107Trp)]

NM_001253852.3(AP4B1):c.319C>T (p.Arg107Trp)

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.319C>T (p.Arg107Trp)

HGVS:

NC_000001.11:g.113902657G>A
NG_031901.1:g.7463C>T
NG_057565.1:g.3039G>A
NM_001253852.3:c.319C>TMANE SELECT
NM_001253853.3:c.22C>T
NM_001308312.2:c.113+1948C>T
NM_006594.5:c.319C>T
NP_001240781.1:p.Arg107Trp
NP_001240782.1:p.Arg8Trp
NP_006585.2:p.Arg107Trp
LRG_1219:g.3039G>A
NC_000001.10:g.114445279G>A
NC_000001.10:g.114445279G>A
NM_006594.4:c.319C>T

Protein change:

R107W

Links:

dbSNP: rs74361335

NCBI 1000 Genomes Browser:

rs74361335

Molecular consequence:

NM_001308312.2:c.113+1948C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001253852.3:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001253853.3:c.22C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006594.5:c.319C>T - 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

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
SCV001190891	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI WGS	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 11, 2019)	paternal	research	PubMed (1) [See all records that cite this PMID]
SCV002153584	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004050695	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004363634	Institute of Immunology and Genetics Kaiserslautern	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 2, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	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
not provided	paternal	yes	1	not provided	not provided	1	not provided	research

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

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 HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI WGS, SCV001190891.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002153584.2

#	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 tryptophan at codon 107 of the AP4B1 protein (p.Arg107Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs74361335, ExAC 0.003%). 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: 828196). 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

From Genome-Nilou Lab, SCV004050695.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Immunology and Genetics Kaiserslautern, SCV004363634.1

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

Description

ACMG Criteria: PM2, PP3; Variant was found in homozygous state

#	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