NM_001611.5(ACP5):c.632T>C (p.Ile211Thr) AND Spondyloenchondrodysplasia with immune dysregulation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 8, 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:: RCV001214543.6

Allele description [Variation Report for NM_001611.5(ACP5):c.632T>C (p.Ile211Thr)]

NM_001611.5(ACP5):c.632T>C (p.Ile211Thr)

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.632T>C (p.Ile211Thr)

HGVS:

NC_000019.10:g.11576346A>G
NG_028127.1:g.7641T>C
NM_001111034.3:c.632T>C
NM_001111035.3:c.632T>C
NM_001111036.3:c.632T>C
NM_001322023.2:c.632T>C
NM_001611.5:c.632T>CMANE SELECT
NP_001104504.1:p.Ile211Thr
NP_001104505.1:p.Ile211Thr
NP_001104506.1:p.Ile211Thr
NP_001308952.1:p.Ile211Thr
NP_001602.1:p.Ile211Thr
LRG_1218t1:c.632T>C
LRG_1218:g.7641T>C
LRG_1218p1:p.Ile211Thr
NC_000019.9:g.11687161A>G
NM_001111035.2:c.632T>C

Protein change:

I211T

Links:

dbSNP: rs770788576

NCBI 1000 Genomes Browser:

rs770788576

Molecular consequence:

NM_001111034.3:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001111035.3:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001111036.3:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322023.2:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001611.5:c.632T>C - 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
SCV001386228	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 8, 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

SCV001386228

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 8, 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, SCV001386228.4

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

Description

This variant has not been reported in the literature in individuals with ACP5-related conditions. This variant is present in population databases (rs770788576, ExAC 0.002%). This sequence change replaces isoleucine with threonine at codon 211 of the ACP5 protein (p.Ile211Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies.

#	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: Feb 28, 2024

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