NM_001611.5(ACP5):c.517G>A (p.Glu173Lys) AND Spondyloenchondrodysplasia with immune dysregulation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 27, 2020
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:: RCV001301396.5

Allele description [Variation Report for NM_001611.5(ACP5):c.517G>A (p.Glu173Lys)]

NM_001611.5(ACP5):c.517G>A (p.Glu173Lys)

Gene:

ACP5:acid phosphatase 5, tartrate resistant [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001611.5(ACP5):c.517G>A (p.Glu173Lys)

HGVS:

NC_000019.10:g.11576461C>T
NG_028127.1:g.7526G>A
NM_001111034.3:c.517G>A
NM_001111035.3:c.517G>A
NM_001111036.3:c.517G>A
NM_001322023.2:c.517G>A
NM_001611.5:c.517G>AMANE SELECT
NP_001104504.1:p.Glu173Lys
NP_001104505.1:p.Glu173Lys
NP_001104506.1:p.Glu173Lys
NP_001308952.1:p.Glu173Lys
NP_001602.1:p.Glu173Lys
LRG_1218t1:c.517G>A
LRG_1218:g.7526G>A
LRG_1218p1:p.Glu173Lys
NC_000019.9:g.11687276C>T

Protein change:

E173K

Links:

dbSNP: rs1973158210

NCBI 1000 Genomes Browser:

rs1973158210

Molecular consequence:

NM_001111034.3:c.517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001111035.3:c.517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001111036.3:c.517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322023.2:c.517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001611.5:c.517G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)
Synonyms:: COMBINED IMMUNODEFICIENCY WITH AUTOIMMUNITY AND SPONDYLOMETAPHYSEAL DYSPLASIA; ROIFMAN IMMUNOSKELETAL SYNDROME; SPONDYLOENCHONDRODYSPLASIA WITH OR WITHOUT IMMUNE DYSREGULATION
Identifiers:: MONDO: MONDO:0011939; MedGen: C1842763; OMIM: 607944

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001490563	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 27, 2020)	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

SCV001490563

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 27, 2020)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001490563.3

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

Description

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. 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 lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ACP5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 173 of the ACP5 protein (p.Glu173Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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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