NM_024818.6(UBA5):c.215G>A (p.Arg72His) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000998136.19

Allele description [Variation Report for NM_024818.6(UBA5):c.215G>A (p.Arg72His)]

NM_024818.6(UBA5):c.215G>A (p.Arg72His)

Genes:

NPHP3-ACAD11:NPHP3-ACAD11 readthrough (NMD candidate) [Gene - HGNC]
UBA5:ubiquitin like modifier activating enzyme 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_024818.6(UBA5):c.215G>A (p.Arg72His)

HGVS:

NC_000003.12:g.132665991G>A
NG_052968.1:g.16546G>A
NM_001320210.2:c.47G>A
NM_001321238.2:c.28-2827G>A
NM_001321239.1:c.-39-2827G>A
NM_024818.6:c.215G>AMANE SELECT
NM_198329.4:c.47G>A
NP_001307139.1:p.Arg16His
NP_079094.1:p.Arg72His
NP_938143.1:p.Arg16His
NC_000003.11:g.132384835G>A
NC_000003.11:g.132384835G>A
NM_024818.3:c.215G>A

Protein change:

R16H

Links:

dbSNP: rs150313260

NCBI 1000 Genomes Browser:

rs150313260

Molecular consequence:

NM_001321238.2:c.28-2827G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001321239.1:c.-39-2827G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001320210.2:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024818.6:c.215G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198329.4:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001154064	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (May 1, 2019)	germline	clinical testing	Citation Link,
SCV002306824	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32371413, 28492532
SCV004169055	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 2, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001154064

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(May 1, 2019)

germline

clinical testing

Citation Link,

SCV002306824

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004169055

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	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

Citations

PubMed

Disease-associated mosaic variation in clinical exome sequencing: a two-year pediatric tertiary care experience.

Miller CR, Lee K, Pfau RB, Reshmi SC, Corsmeier DJ, Hashimoto S, Dave-Wala A, Jayaraman V, Koboldt D, Matthews T, Mouhlas D, Stein M, McKinney A, Grossman T, Kelly BJ, White P, Magrini V, Wilson RK, Mardis ER, Cottrell CE.

Cold Spring Harb Mol Case Stud. 2020 Jun 12;6(3). doi:pii: a005231. 10.1101/mcs.a005231. Print 2020 Jun.

PubMed [citation]

PMID:: 32371413
PMCID:: PMC7304353

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 CeGaT Center for Human Genetics Tuebingen, SCV001154064.21

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

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

From Invitae, SCV002306824.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 72 of the UBA5 protein (p.Arg72His). This variant is present in population databases (rs150313260, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (PMID: 32371413). ClinVar contains an entry for this variant (Variation ID: 809545). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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 GeneDx, SCV004169055.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27397505, 28404951, 32579932, 32371413)

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

Last Updated: Apr 15, 2024

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