NM_003764.4(STX11):c.83C>A (p.Ser28Ter) AND Familial hemophagocytic lymphohistiocytosis 4

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001925648.5

Allele description [Variation Report for NM_003764.4(STX11):c.83C>A (p.Ser28Ter)]

NM_003764.4(STX11):c.83C>A (p.Ser28Ter)

Gene:

STX11:syntaxin 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q24.2

Genomic location:

Preferred name:

NM_003764.4(STX11):c.83C>A (p.Ser28Ter)

HGVS:

NC_000006.12:g.144186710C>A
NG_007613.1:g.41194C>A
NM_003764.4:c.83C>AMANE SELECT
NP_003755.2:p.Ser28Ter
LRG_113:g.41194C>A
NC_000006.11:g.144507847C>A

Protein change:

S28*

Links:

dbSNP: rs143547259

NCBI 1000 Genomes Browser:

rs143547259

Molecular consequence:

NM_003764.4:c.83C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial hemophagocytic lymphohistiocytosis 4 (FHL4)
Identifiers:: MONDO: MONDO:0011336; MedGen: C1863728; Orphanet: 540; OMIM: 603552

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180388	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24459464, 26004995, 28492532
SCV004205614	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002180388

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004205614

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 28, 2023)

unknown

clinical testing

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

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

Citations

PubMed

An N-Terminal Missense Mutation in STX11 Causative of FHL4 Abrogates Syntaxin-11 Binding to Munc18-2.

Müller ML, Chiang SC, Meeths M, Tesi B, Entesarian M, Nilsson D, Wood SM, Nordenskjöld M, Henter JI, Naqvi A, Bryceson YT.

Front Immunol. 2014 Jan 14;4:515. doi: 10.3389/fimmu.2013.00515.

PubMed [citation]

PMID:: 24459464
PMCID:: PMC3890652

Cerebellar swelling due to familial hemophagocytic lymphohistiocytosis: An unusual presentation.

Khan SG, Binmahfoodh M, Alali M, Bayoumy M, Al-Said Y, Kayyali HR.

Eur J Paediatr Neurol. 2015 Sep;19(5):603-6. doi: 10.1016/j.ejpn.2015.04.009. Epub 2015 May 14.

PubMed [citation]

PMID:: 26004995

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002180388.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Ser28*) in the STX11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 260 amino acid(s) of the STX11 protein. This variant is present in population databases (rs143547259, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with STX11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1412986). This variant disrupts a region of the STX11 protein in which other variant(s) (p.Leu58Pro) have been determined to be pathogenic (PMID: 24459464, 26004995; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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

From Baylor Genetics, SCV004205614.1

#	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

Last Updated: Sep 29, 2024

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