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NM_007347.5(AP4E1):c.211A>G (p.Thr71Ala) AND Spastic paraplegia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 28, 2021
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:
RCV002042715.5

Allele description [Variation Report for NM_007347.5(AP4E1):c.211A>G (p.Thr71Ala)]

NM_007347.5(AP4E1):c.211A>G (p.Thr71Ala)

Gene:
AP4E1:adaptor related protein complex 4 subunit epsilon 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.2
Genomic location:
Preferred name:
NM_007347.5(AP4E1):c.211A>G (p.Thr71Ala)
HGVS:
  • NC_000015.10:g.50912138A>G
  • NG_031875.2:g.8467A>G
  • NM_001252127.2:c.-38A>G
  • NM_007347.5:c.211A>GMANE SELECT
  • NP_031373.2:p.Thr71Ala
  • LRG_732t1:c.211A>G
  • LRG_732:g.8467A>G
  • LRG_732p1:p.Thr71Ala
  • NC_000015.9:g.51204335A>G
Protein change:
T71A
Links:
dbSNP: rs1490232988
NCBI 1000 Genomes Browser:
rs1490232988
Molecular consequence:
  • NM_001252127.2:c.-38A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_007347.5:c.211A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spastic paraplegia
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002289797Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 28, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV002289797.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces threonine with alanine at codon 71 of the AP4E1 protein (p.Thr71Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with AP4E1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024