NM_000295.5(SERPINA1):c.787del (p.Val263fs) AND Alpha-1-antitrypsin deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 19, 2023
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:: RCV001951534.4

Allele description [Variation Report for NM_000295.5(SERPINA1):c.787del (p.Val263fs)]

NM_000295.5(SERPINA1):c.787del (p.Val263fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_000295.5(SERPINA1):c.787del (p.Val263fs)

HGVS:

NC_000014.9:g.94381003del
NG_008290.1:g.14692del
NM_000295.5:c.787delMANE SELECT
NM_001002235.3:c.787del
NM_001002236.3:c.787del
NM_001127700.2:c.787del
NM_001127701.2:c.787del
NM_001127702.2:c.787del
NM_001127703.2:c.787del
NM_001127704.2:c.787del
NM_001127705.2:c.787del
NM_001127706.2:c.787del
NM_001127707.2:c.787del
NP_000286.3:p.Val263fs
NP_001002235.1:p.Val263fs
NP_001002236.1:p.Val263fs
NP_001121172.1:p.Val263fs
NP_001121173.1:p.Val263fs
NP_001121174.1:p.Val263fs
NP_001121175.1:p.Val263fs
NP_001121176.1:p.Val263fs
NP_001121177.1:p.Val263fs
NP_001121178.1:p.Val263fs
NP_001121179.1:p.Val263fs
LRG_575t1:c.787del
LRG_575:g.14692del
LRG_575p1:p.Val263fs
NC_000014.8:g.94847338del
NC_000014.8:g.94847340del

Protein change:

V263fs

Links:

dbSNP: rs1200349975

NCBI 1000 Genomes Browser:

rs1200349975

Molecular consequence:

NM_000295.5:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001002235.3:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001002236.3:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127700.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127701.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127702.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127703.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127704.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127705.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127706.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127707.2:c.787del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Zanclea alba isolate GMx 16S ribosomal RNA gene, partial sequence; mitochondrial
Zanclea alba isolate GMx 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|1270025917|gb|MF538731.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002244574	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 19, 2023)	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

SCV002244574

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 19, 2023)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002244574.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1460301). This sequence change creates a premature translational stop signal (p.Val263Cysfs*3) in the SERPINA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SERPINA1 are known to be pathogenic (PMID: 25425243). This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with emphysema (PMID: 25425243). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

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