NM_000488.4(SERPINC1):c.408+4C>T AND Hereditary antithrombin deficiency

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jul 25, 2023
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:: RCV001101590.6

Allele description [Variation Report for NM_000488.4(SERPINC1):c.408+4C>T]

NM_000488.4(SERPINC1):c.408+4C>T

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.408+4C>T

HGVS:

NC_000001.11:g.173914549G>A
NG_012462.1:g.7830C>T
NM_000488.4:c.408+4C>TMANE SELECT
NM_001365052.2:c.264+4C>T
NM_001386302.1:c.408+4C>T
NM_001386303.1:c.489+4C>T
NM_001386304.1:c.408+4C>T
NM_001386305.1:c.408+4C>T
NM_001386306.1:c.408+4C>T
LRG_577t1:c.408+4C>T
LRG_577:g.7830C>T
NC_000001.10:g.173883687G>A
NM_000488.3:c.408+4C>T

Links:

dbSNP: rs201551398

NCBI 1000 Genomes Browser:

rs201551398

Molecular consequence:

NM_000488.4:c.408+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001365052.2:c.264+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386302.1:c.408+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386303.1:c.489+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386304.1:c.408+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386305.1:c.408+4C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386306.1:c.408+4C>T - 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
SCV001258213	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV002785974	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 23, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004037385	Clingen Thrombosis Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen ACMG Specifications SERPINC1 V1.0.0)	Likely benign (Jul 25, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001258213

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV002785974

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 23, 2021)

unknown

clinical testing

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

SCV004037385

Clingen Thrombosis Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen ACMG Specifications SERPINC1 V1.0.0)

Likely benign
(Jul 25, 2023)

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001258213.1

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

Description

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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002785974.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clingen Thrombosis Variant Curation Expert Panel, ClinGen, SCV004037385.1

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

Description

The NM_000488.4(SERPINC1):c.408+4C>T variant is an intronic variant reported at a POPMAX FAF of 0.0003794 in the South Asian population (18/30616 alleles) meeting BS1 criteria. SpliceAI and VarSEAK predict no splicing impact for this variant; however the nucleotide may be conserved based on PhyloP and PhastCons scores (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for AT Deficiency for SERPINC1: BS1, BP4.

#	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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