NM_005859.5(PURA):c.493G>A (p.Gly165Ser) AND PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 2, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000704255.14

Allele description [Variation Report for NM_005859.5(PURA):c.493G>A (p.Gly165Ser)]

NM_005859.5(PURA):c.493G>A (p.Gly165Ser)

Gene:

PURA:purine rich element binding protein A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_005859.5(PURA):c.493G>A (p.Gly165Ser)

HGVS:

NC_000005.10:g.140114674G>A
NG_041813.1:g.5552G>A
NM_005859.5:c.493G>AMANE SELECT
NP_005850.1:p.Gly165Ser
NC_000005.9:g.139494259G>A
NM_005859.4:c.493G>A
p.G165S

Protein change:

G165S

Links:

dbSNP: rs1561793272

NCBI 1000 Genomes Browser:

rs1561793272

Molecular consequence:

NM_005859.5:c.493G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (NEDRIHF)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH NEONATAL RESPIRATORY INSUFFICIENCY, HYPOTONIA, AND FEEDING DIFFICULTIES
Identifiers:: MedGen: C4015357; Orphanet: 438216; OMIM: 616158

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000833197	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001245597	Undiagnosed Diseases Network, NIH	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 2, 2019)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001520922	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 2, 2019)	de novo	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

SCV000833197

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2019)

germline

clinical testing

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

SCV001245597

Undiagnosed Diseases Network, NIH

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 2, 2019)

de novo

clinical testing

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

SCV001520922

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 2, 2019)

de novo

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	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Causasians	de novo	yes	1	1	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000833197.6

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PURA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 165 of the PURA protein (p.Gly165Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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

From Undiagnosed Diseases Network, NIH, SCV001245597.1

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

Description

Structural biology analysis predicts missense change will be damaging to protein function

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	blood	not provided		1	not provided	1	not provided

From Baylor Genetics, SCV001520922.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine