NM_007347.5(AP4E1):c.2470G>A (p.Val824Met) AND Spastic paraplegia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 8, 2024
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:: RCV003589909.2

Allele description [Variation Report for NM_007347.5(AP4E1):c.2470G>A (p.Val824Met)]

NM_007347.5(AP4E1):c.2470G>A (p.Val824Met)

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.2470G>A (p.Val824Met)

HGVS:

NC_000015.10:g.50997449G>A
NG_031875.2:g.93778G>A
NM_001252127.2:c.2245G>A
NM_007347.5:c.2470G>AMANE SELECT
NP_001239056.1:p.Val749Met
NP_031373.2:p.Val824Met
LRG_732t1:c.2470G>A
LRG_732:g.93778G>A
LRG_732p1:p.Val824Met
NC_000015.9:g.51289646G>A

Protein change:

V749M

Molecular consequence:

NM_001252127.2:c.2245G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007347.5:c.2470G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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zinc transporter ZIP3 isoform X3 [Varanus komodoensis]
zinc transporter ZIP3 isoform X3 [Varanus komodoensis]
gi|2118041516|ref|XP_044275040.1|

Protein
zinc transporter ZIP3 isoform X1 [Varanus komodoensis]
zinc transporter ZIP3 isoform X1 [Varanus komodoensis]
gi|2118041508|ref|XP_044275036.1|

Protein
chemokine (C-C motif) ligand 14, partial [Ochotona pallasi]
chemokine (C-C motif) ligand 14, partial [Ochotona pallasi]
gi|805489815|gb|AKB91119.1|

Protein
TRMT1-like protein isoform 1 [Homo sapiens]
TRMT1-like protein isoform 1 [Homo sapiens]
gi|163792194|ref|NP_112196.3|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004259756	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 8, 2024)	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

SCV004259756

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 8, 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	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, SCV004259756.1

#	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 valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 824 of the AP4E1 protein (p.Val824Met). This variant is not present in population databases (gnomAD 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine 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.

#	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

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