ClinVar contains an entry for this variant (Variation ID: 161390). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINC1 protein function. This missense change has been observed in individual(s) with AT deficiency (PMID: 22627591). This variant is present in population databases (rs372820797, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 296 of the SERPINC1 protein (p.Ala296Pro).
ClinVar Genomic variation as it relates to human health
NM_000488.4(SERPINC1):c.886G>C (p.Ala296Pro)
Germline
Classification
Help
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.
(5)
Help
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.
Uncertain significance
5
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000488.4(SERPINC1):c.886G>C (p.Ala296Pro)
Variation ID: 161390 Accession: VCV000161390.13
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q25.1 1: 173909819 (GRCh38) [ NCBI UCSC ] 1: 173878957 (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 Dec 7, 2014 Feb 14, 2024 Oct 23, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000488.4:c.886G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000479.1:p.Ala296Pro missense NM_001365052.2:c.742G>C NP_001351981.1:p.Ala248Pro missense NM_001386302.1:c.1009G>C NP_001373231.1:p.Ala337Pro missense NM_001386303.1:c.967G>C NP_001373232.1:p.Ala323Pro missense NM_001386304.1:c.865G>C NP_001373233.1:p.Ala289Pro missense NM_001386305.1:c.829G>C NP_001373234.1:p.Ala277Pro missense NM_001386306.1:c.670G>C NP_001373235.1:p.Ala224Pro missense NC_000001.11:g.173909819C>G NC_000001.10:g.173878957C>G NG_012462.1:g.12560G>C LRG_577:g.12560G>C LRG_577t1:c.886G>C LRG_577p1:p.Ala296Pro - Protein change
- A296P, A248P, A224P, A277P, A289P, A323P, A337P
- Other names
- -
- Canonical SPDI
- NC_000001.11:173909818:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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.
-
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| SERPINC1 | - | - |
GRCh38 GRCh37 |
382 | 441 | |
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. |
|---|---|---|---|---|
| Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
|
Oct 23, 2022 | RCV001099621.19 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary antithrombin deficiency
Affected status: yes
Allele origin:
germline
|
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV004014040.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023
Comment:
Submitted to GoldVariant by Kathleen Freson, Center for Molecular and Vascular Biology, Leuven, Belgium
|
Observation 1:
Clinical Features:
Venous sinus thrombosis (present)
Zygosity: Single Heterozygote
Observation 2:
Clinical Features:
Deep vein thrombosis, pulmonary embolism (present)
Zygosity: Single Heterozygote
|
|
|
Uncertain significance
(Oct 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary antithrombin deficiency
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002788339.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Uncertain significance
(Oct 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary antithrombin deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003270931.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 161390). In summary, the available evidence is currently insufficient to determine the role of this variant … (more)
ClinVar contains an entry for this variant (Variation ID: 161390). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINC1 protein function. This missense change has been observed in individual(s) with AT deficiency (PMID: 22627591). This variant is present in population databases (rs372820797, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 296 of the SERPINC1 protein (p.Ala296Pro). (less)
|
|
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Uncertain significance
(Apr 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary antithrombin deficiency
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001256093.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
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Uncertain significance
(Jun 01, 2014)
|
no assertion criteria provided
Method: research
|
Antithrombin deficiency
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190629.1 First in ClinVar: Dec 07, 2014 Last updated: Dec 07, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
|
|
Comment:
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
ClinVar contains an entry for this variant (Variation ID: 161390). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SERPINC1 protein function. This missense change has been observed in individual(s) with AT deficiency (PMID: 22627591). This variant is present in population databases (rs372820797, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 296 of the SERPINC1 protein (p.Ala296Pro).
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort. | Caspers M | Thrombosis and haemostasis | 2012 | PMID: 22627591 |
Text-mined citations for rs372820797 ...
HelpThese 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 Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.