NM_032634.4(PIGO):c.1591G>A (p.Ala531Thr) AND Hyperphosphatasia with intellectual disability syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 16, 2019
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:: RCV001068711.9

Allele description [Variation Report for NM_032634.4(PIGO):c.1591G>A (p.Ala531Thr)]

NM_032634.4(PIGO):c.1591G>A (p.Ala531Thr)

Gene:

PIGO:phosphatidylinositol glycan anchor biosynthesis class O [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_032634.4(PIGO):c.1591G>A (p.Ala531Thr)

HGVS:

NC_000009.12:g.35092296C>T
NG_031990.1:g.9306G>A
NM_001201484.2:c.1344+247G>A
NM_032634.4:c.1591G>AMANE SELECT
NM_152850.4:c.1344+247G>A
NP_116023.2:p.Ala531Thr
NC_000009.11:g.35092293C>T
NM_032634.3:c.1591G>A

Protein change:

A531T

Links:

dbSNP: rs1416430595

NCBI 1000 Genomes Browser:

rs1416430595

Molecular consequence:

NM_001201484.2:c.1344+247G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_152850.4:c.1344+247G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_032634.4:c.1591G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyperphosphatasia with intellectual disability syndrome 2 (HPMRS2)
Synonyms:: GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 6; HYPERPHOSPHATASIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME 2
Identifiers:: MONDO: MONDO:0013882; MedGen: C3553637; Orphanet: 247262; OMIM: 614749

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001233838	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 16, 2019)	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

SCV001233838

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 16, 2019)

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, SCV001233838.6

#	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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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 PIGO-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 531 of the PIGO protein (p.Ala531Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine.

#	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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