VCV000017992.5 - ClinVar

NM_001127701.1(SERPINA1):c.230C>T (p.Ser77Phe)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001127701.1(SERPINA1):c.230C>T (p.Ser77Phe)

Variation ID: 17992 Accession: VCV000017992.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q32.13 14: 94383008 (GRCh38) [ NCBI UCSC ] 14: 94849345 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 29, 2015	Dec 24, 2022	Dec 18, 2014

HGVS

Nucleotide	Protein	Molecular consequence
NM_000295.5:c.230C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000286.3:p.Ser77Phe	missense
NM_001002235.3:c.230C>T	NP_001002235.1:p.Ser77Phe	missense
NM_001002236.3:c.230C>T	NP_001002236.1:p.Ser77Phe	missense
NM_001127700.2:c.230C>T	NP_001121172.1:p.Ser77Phe	missense
NM_001127701.2:c.230C>T	NP_001121173.1:p.Ser77Phe	missense
NM_001127702.2:c.230C>T	NP_001121174.1:p.Ser77Phe	missense
NM_001127703.2:c.230C>T	NP_001121175.1:p.Ser77Phe	missense
NM_001127704.2:c.230C>T	NP_001121176.1:p.Ser77Phe	missense
NM_001127705.2:c.230C>T	NP_001121177.1:p.Ser77Phe	missense
NM_001127706.2:c.230C>T	NP_001121178.1:p.Ser77Phe	missense
NM_001127707.2:c.230C>T	NP_001121179.1:p.Ser77Phe	missense
NC_000014.9:g.94383008G>A
NC_000014.8:g.94849345G>A
NG_008290.1:g.12685C>T
LRG_575:g.12685C>T
LRG_575t1:c.230C>T	LRG_575p1:p.Ser77Phe
	P01009:p.Ser77Phe

... more HGVS ... less HGVS

Protein change

S77F

Other names

S53F
PI*Siiyama
SERPINA1, SER53PHE
Siiyama

Canonical SPDI

NC_000014.9:94383007:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

effect on catalytic protein function; Variation Ontology [ VariO:0008]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

ClinGen: CA127738 UniProtKB: P01009#VAR_006985 OMIM: 107400.0039 dbSNP: rs55819880 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SERPINA1		-	-	GRCh38 GRCh38 GRCh37	483	518

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
PI S(IIYAMA)	other (1)	no assertion criteria provided	Jul 15, 2016	RCV000019608.11
Alpha-1-antitrypsin deficiency	Pathogenic (3)	criteria provided, single submitter	Dec 18, 2014	RCV000169508.16

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Dec 18, 2014)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: literature only	Alpha-1-antitrypsin deficiency (Autosomal recessive inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000220973.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022	Publications: PubMed (6) PubMed: 8340361‚ 22016686‚ 8358043‚ 15486938‚ 8520784‚ 1905728
other (Jul 15, 2016)	no assertion criteria provided Method: literature only	PI S(IIYAMA) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000039906.2 First in ClinVar: Apr 04, 2013 Last updated: Jul 19, 2016	Publications: PubMed (2) PubMed: 8358043‚ 2309708 Comment on evidence: In a 32-year-old Japanese male with pulmonary emphysema, Yuasa et al. (1993) demonstrated homozygosity for a C-to-T transition at codon 53 resulting in substitution of … (more) In a 32-year-old Japanese male with pulmonary emphysema, Yuasa et al. (1993) demonstrated homozygosity for a C-to-T transition at codon 53 resulting in substitution of phenylalanine for serine. They commented on the fact that, in Japanese, deficiency in null alleles at the AAT locus are extremely rare and PI*Z, which occurs at polymorphic frequencies in Caucasians, has not been reported. The only other Japanese case of AAT deficiency was that due to PI M(Nichinan) (107400.0017) reported by Matsunaga et al. (1990). (less)
Pathogenic (Dec 08, 2014)	no assertion criteria provided Method: curation	Alpha-1-antitrypsin deficiency Affected status: yes Allele origin: germline	Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital Accession: SCV000608309.1 First in ClinVar: Oct 26, 2017 Last updated: Oct 26, 2017 Comment: Rare deficiency allele in cis with c.863A>T	Publications: PubMed (1) PubMed: 8358043 Comment: Reduced enzyme activity Clinical Features: emphysema (present) , COPD (present)
not provided (-)	no classification provided Method: literature only	Alpha-1-antitrypsin deficiency Affected status: yes Allele origin: germline	GeneReviews Accession: SCV000256615.2 First in ClinVar: Mar 29, 2015 Last updated: Oct 01, 2022	Publications: BookShelf: NBK1519 BookShelf: NBK1519

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
effect on catalytic protein function (VariO:0008)			Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital Accession: SCV000608309.1	Publications PubMed (1)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Alpha-1 Antitrypsin Deficiency.	Adam MP	-	2023	PMID: 20301692
Identification of compound heterozygous mutation in a Korean patient with alpha 1-antitrypsin deficiency.	Ko DH	The Korean journal of laboratory medicine	2011	PMID: 22016686
Differential detection of PAS-positive inclusions formed by the Z, Siiyama, and Mmalton variants of alpha1-antitrypsin.	Janciauskiene S	Hepatology (Baltimore, Md.)	2004	PMID: 15486938
Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.	Seyama K	American journal of respiratory and critical care medicine	1995	PMID: 8520784
PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan.	Yuasa I	The Japanese journal of human genetics	1993	PMID: 8358043
Alpha 1-antitrypsin Siiyama (Ser53-->Phe). Further evidence for intracellular loop-sheet polymerization.	Lomas DA	The Journal of biological chemistry	1993	PMID: 8340361
Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone.	Seyama K	The Journal of biological chemistry	1991	PMID: 1905728
Molecular analysis of the gene of the alpha 1-antitrypsin deficiency variant, Mnichinan.	Matsunaga E	American journal of human genetics	1990	PMID: 2309708

Text-mined citations for rs55819880 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 27, 2024

ClinVar Genomic variation as it relates to human health

NM_001127701.1(SERPINA1):c.230C>T (p.Ser77Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs55819880 ...