NM_000295.5(SERPINA1):c.841G>T (p.Glu281Ter) AND Alpha-1-antitrypsin deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 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:: RCV001065386.7

Allele description [Variation Report for NM_000295.5(SERPINA1):c.841G>T (p.Glu281Ter)]

NM_000295.5(SERPINA1):c.841G>T (p.Glu281Ter)

Gene:

SERPINA1:serpin family A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_000295.5(SERPINA1):c.841G>T (p.Glu281Ter)

HGVS:

NC_000014.9:g.94380947C>A
NG_008290.1:g.14746G>T
NM_000295.5:c.841G>TMANE SELECT
NM_001002235.3:c.841G>T
NM_001002236.3:c.841G>T
NM_001127700.2:c.841G>T
NM_001127701.2:c.841G>T
NM_001127702.2:c.841G>T
NM_001127703.2:c.841G>T
NM_001127704.2:c.841G>T
NM_001127705.2:c.841G>T
NM_001127706.2:c.841G>T
NM_001127707.2:c.841G>T
NP_000286.3:p.Glu281Ter
NP_001002235.1:p.Glu281Ter
NP_001002236.1:p.Glu281Ter
NP_001121172.1:p.Glu281Ter
NP_001121173.1:p.Glu281Ter
NP_001121174.1:p.Glu281Ter
NP_001121175.1:p.Glu281Ter
NP_001121176.1:p.Glu281Ter
NP_001121177.1:p.Glu281Ter
NP_001121178.1:p.Glu281Ter
NP_001121179.1:p.Glu281Ter
LRG_575t1:c.841G>T
LRG_575:g.14746G>T
LRG_575p1:p.Glu281Ter
NC_000014.8:g.94847284C>A
NM_000295.4:c.841G>T

Protein change:

E281*

Links:

dbSNP: rs760917668

NCBI 1000 Genomes Browser:

rs760917668

Molecular consequence:

NM_000295.5:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001002235.3:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001002236.3:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127700.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127701.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127702.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127703.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127704.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127705.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127706.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127707.2:c.841G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Alpha-1-antitrypsin deficiency (A1ATD)
Synonyms:: AAT deficiency; A1AT deficiency; Alpha1-Antitrypsin Deficiency
Identifiers:: MONDO: MONDO:0013282; MedGen: C0221757; Orphanet: 60; OMIM: 613490

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001230342	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 12, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25425243, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001230342

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 12, 2019)

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

Identification and characterisation of eight novel SERPINA1 Null mutations.

Ferrarotti I, Carroll TP, Ottaviani S, Fra AM, O'Brien G, Molloy K, Corda L, Medicina D, Curran DR, McElvaney NG, Luisetti M.

Orphanet J Rare Dis. 2014 Nov 26;9:172. doi: 10.1186/s13023-014-0172-y.

PubMed [citation]

PMID:: 25425243
PMCID:: PMC4255440

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, SCV001230342.5

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

Description

Loss-of-function variants in SERPINA1 are known to be pathogenic (PMID: 25425243). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with alpha-1 antitrypsin deficiency(PMID:¬†25425243). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu281*) in the SERPINA1 gene. It is expected to result in an absent or disrupted protein product.

#	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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