NM_000488.4(SERPINC1):c.1219-8A>G AND Hereditary antithrombin deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 19, 2024
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV002715013.4

Allele description [Variation Report for NM_000488.4(SERPINC1):c.1219-8A>G]

NM_000488.4(SERPINC1):c.1219-8A>G

Gene:

SERPINC1:serpin family C member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.1

Genomic location:

Preferred name:

NM_000488.4(SERPINC1):c.1219-8A>G

HGVS:

NC_000001.11:g.173904073T>C
NG_012462.1:g.18306A>G
NM_000488.4:c.1219-8A>GMANE SELECT
NM_001365052.2:c.1075-8A>G
NM_001386302.1:c.1342-8A>G
NM_001386303.1:c.1300-8A>G
NM_001386304.1:c.1198-8A>G
NM_001386305.1:c.1162-8A>G
NM_001386306.1:c.1003-8A>G
LRG_577:g.18306A>G
NC_000001.10:g.173873211T>C

Molecular consequence:

NM_000488.4:c.1219-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001365052.2:c.1075-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386302.1:c.1342-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386303.1:c.1300-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386304.1:c.1198-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386305.1:c.1162-8A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386306.1:c.1003-8A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hereditary antithrombin deficiency (AT3D)
Synonyms:: Antithrombin III deficiency; Thrombophilia due to antithrombin III deficiency; Reduced antithrombin III activity; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013144; MedGen: C0272375; OMIM: 613118; Human Phenotype Ontology: HP:0001976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002998595	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Feb 4, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005061620	Clingen Thrombosis Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen ACMG Specifications SERPINC1 V1.0.0)	Uncertain Significance (Feb 19, 2024)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002998595

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Feb 4, 2022)

germline

clinical testing

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

SCV005061620

Clingen Thrombosis Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen ACMG Specifications SERPINC1 V1.0.0)

Uncertain Significance
(Feb 19, 2024)

germline

curation

Citation Link

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, curation

Citations

PubMed

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, SCV002998595.2

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

#	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

From Clingen Thrombosis Variant Curation Expert Panel, ClinGen, SCV005061620.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.1219-8A>G (NM_000488.4) variant in SERPINC1 does not code for protein sequence. SpliceAI predicts no splicing impact for this variant meeting BP4. The variant is not predicted to cause a splicing impact and the nucleotide is weakly/moderately conserved with a PhyloP score of -0.864 and a PhastCons score of 0 meeting BP7 criteria (PhyloP < 0.1). In summary, this variant meets criteria to be classified as variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BP4, BP7, PM2_Supporting.

#	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: Oct 8, 2024

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