NM_004371.4(COPA):c.772C>T (p.His258Tyr) AND Autoimmune interstitial lung disease-arthritis syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 10, 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:: RCV001308865.6

Allele description

NM_004371.4(COPA):c.772C>T (p.His258Tyr)

Gene:

COPA:COPI coat complex subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.2

Genomic location:

Preferred name:

NM_004371.4(COPA):c.772C>T (p.His258Tyr)

HGVS:

NC_000001.11:g.160314060G>A
NG_050927.1:g.34505C>T
NM_001098398.2:c.772C>T
NM_004371.4:c.772C>TMANE SELECT
NP_001091868.1:p.His258Tyr
NP_004362.2:p.His258Tyr
LRG_1336t1:c.772C>T
LRG_1336:g.34505C>T
LRG_1336p1:p.His258Tyr
NC_000001.10:g.160283850G>A

Protein change:

H258Y

Links:

dbSNP: rs1659060523

NCBI 1000 Genomes Browser:

rs1659060523

Molecular consequence:

NM_001098398.2:c.772C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004371.4:c.772C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autoimmune interstitial lung disease-arthritis syndrome
Synonyms:: Autoimmune interstitial lung, joint, and kidney disease
Identifiers:: MONDO: MONDO:0014629; MedGen: C5243948; Orphanet: 444092; OMIM: 616414

Recent activity

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sickle tail protein homolog isoform X33 [Homo sapiens]
sickle tail protein homolog isoform X33 [Homo sapiens]
gi|2462520184|ref|XP_054222329.1|

Protein
sickle tail protein homolog isoform X4 [Homo sapiens]
sickle tail protein homolog isoform X4 [Homo sapiens]
gi|2462520118|ref|XP_054222296.1|

Protein
PREDICTED: Homo sapiens KIAA1217 (KIAA1217), transcript variant X34, mRNA
PREDICTED: Homo sapiens KIAA1217 (KIAA1217), transcript variant X34, mRNA
gi|2462520177|ref|XM_054366351.1|

Nucleotide
PREDICTED: Homo sapiens KIAA1217 (KIAA1217), transcript variant X4, mRNA
PREDICTED: Homo sapiens KIAA1217 (KIAA1217), transcript variant X4, mRNA
gi|2217277932|ref|XM_047425496.1|

Nucleotide
Homo sapiens KIAA1217 (KIAA1217), transcript variant 5, mRNA
Homo sapiens KIAA1217 (KIAA1217), transcript variant 5, mRNA
gi|1890262841|ref|NM_001282768.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001498340	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 10, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27577878, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001498340

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 10, 2020)

germline

clinical testing

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

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

Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders.

Stray-Pedersen A, Sorte HS, Samarakoon P, Gambin T, Chinn IK, Coban Akdemir ZH, Erichsen HC, Forbes LR, Gu S, Yuan B, Jhangiani SN, Muzny DM, Rødningen OK, Sheng Y, Nicholas SK, Noroski LM, Seeborg FO, Davis CM, Canter DL, Mace EM, Vece TJ, Allen CE, et al.

J Allergy Clin Immunol. 2017 Jan;139(1):232-245. doi: 10.1016/j.jaci.2016.05.042. Epub 2016 Jul 16. Erratum in: J Allergy Clin Immunol. 2018 Feb;141(2):832. doi: 10.1016/j.jaci.2017.12.975.

PubMed [citation]

PMID:: 27577878
PMCID:: PMC5222743

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 Invitae, SCV001498340.4

#	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 histidine with tyrosine at codon 258 of the COPA protein (p.His258Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with a primary immunodeficiency (PMID: 27577878). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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

Last Updated: Feb 20, 2024

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