NM_000295.5(SERPINA1):c.538C>T (p.Gln180Ter) AND Alpha-1-antitrypsin deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 12, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000204423.3

Allele description [Variation Report for NM_000295.5(SERPINA1):c.538C>T (p.Gln180Ter)]

NM_000295.5(SERPINA1):c.538C>T (p.Gln180Ter)

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.538C>T (p.Gln180Ter)
HGVS:
  • NC_000014.9:g.94382700G>A
  • NG_008290.1:g.12993C>T
  • NM_000295.5:c.538C>TMANE SELECT
  • NM_001002235.3:c.538C>T
  • NM_001002236.3:c.538C>T
  • NM_001127700.2:c.538C>T
  • NM_001127701.2:c.538C>T
  • NM_001127702.2:c.538C>T
  • NM_001127703.2:c.538C>T
  • NM_001127704.2:c.538C>T
  • NM_001127705.2:c.538C>T
  • NM_001127706.2:c.538C>T
  • NM_001127707.2:c.538C>T
  • NP_000286.3:p.Gln180Ter
  • NP_001002235.1:p.Gln180Ter
  • NP_001002236.1:p.Gln180Ter
  • NP_001121172.1:p.Gln180Ter
  • NP_001121173.1:p.Gln180Ter
  • NP_001121174.1:p.Gln180Ter
  • NP_001121175.1:p.Gln180Ter
  • NP_001121176.1:p.Gln180Ter
  • NP_001121177.1:p.Gln180Ter
  • NP_001121178.1:p.Gln180Ter
  • NP_001121179.1:p.Gln180Ter
  • LRG_575t1:c.538C>T
  • LRG_575:g.12993C>T
  • LRG_575p1:p.Gln180Ter
  • NC_000014.8:g.94849037G>A
  • NM_000295.4:c.538C>T
Protein change:
Q180*
Links:
dbSNP: rs864622051
NCBI 1000 Genomes Browser:
rs864622051
Molecular consequence:
  • NM_000295.5:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001002235.3:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001002236.3:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127700.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127701.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127702.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127703.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127704.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127705.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127706.2:c.538C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001127707.2:c.538C>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000259199HerediLab, Inc.criteria provided, single submitter
Pathogenic
(Aug 17, 2015)
germlineresearch

HerediLab_Assertion_Criteria.pdf,

Citation Link,

SCV000485961Counsylcriteria provided, single submitter
Likely pathogenic
(Mar 8, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001585169Invitaecriteria provided, single submitter
Pathogenic
(Jul 12, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Protein modeling to assess the pathogenicity of rare variants of SERPINA1 in patients suspected of having Alpha 1 Antitrypsin Deficiency.

Kueppers F, Andrake MD, Xu Q, Dunbrack RL Jr, Kim J, Sanders CL.

BMC Med Genet. 2019 Jul 15;20(1):125. doi: 10.1186/s12881-019-0852-5.

PubMed [citation]
PMID:
31307431
PMCID:
PMC6631921

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
See all PubMed Citations (3)

Details of each submission

From HerediLab, Inc., SCV000259199.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000485961.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001585169.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln180*) in the SERPINA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with alpha-1 antitrypsin deficiency (PMID: 31307431). ClinVar contains an entry for this variant (Variation ID: 219364). Loss-of-function variants in SERPINA1 are known to be pathogenic (PMID: 25425243). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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