NM_000043.6(FAS):c.792T>G (p.Asn264Lys) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 3, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001999610.4

Allele description [Variation Report for NM_000043.6(FAS):c.792T>G (p.Asn264Lys)]

NM_000043.6(FAS):c.792T>G (p.Asn264Lys)

Gene:

FAS:Fas cell surface death receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000043.6(FAS):c.792T>G (p.Asn264Lys)

HGVS:

NC_000010.11:g.89014234T>G
NG_009089.2:g.28704T>G
NM_000043.6:c.792T>GMANE SELECT
NM_001320619.2:c.*115T>G
NM_152871.4:c.729T>G
NM_152872.4:c.*104T>G
NP_000034.1:p.Asn264Lys
NP_690610.1:p.Asn243Lys
LRG_134:g.28704T>G
NC_000010.10:g.90773991T>G
NR_028033.4:n.699T>G
NR_028034.4:n.561T>G
NR_028035.4:n.624T>G
NR_028036.4:n.762T>G
NR_135313.2:n.679T>G
NR_135314.2:n.958T>G
NR_135315.2:n.711T>G

Protein change:

N243K

Links:

dbSNP: rs2119446116

NCBI 1000 Genomes Browser:

rs2119446116

Molecular consequence:

NM_001320619.2:c.*115T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152872.4:c.*104T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000043.6:c.792T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_152871.4:c.729T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_028033.4:n.699T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028034.4:n.561T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028035.4:n.624T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028036.4:n.762T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135313.2:n.679T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135314.2:n.958T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135315.2:n.711T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autoimmune lymphoproliferative syndrome type 1 (ALPS)
Synonyms:: Autoimmune lymphoproliferative syndrome type 1, autosomal dominant; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE I, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0011158; MedGen: C1328840; Orphanet: 3261; OMIM: 601859

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002292579	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 3, 2023)	germline	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

SCV002292579

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 3, 2023)

germline

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

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 Invitae, SCV002292579.2

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

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 264 of the FAS protein (p.Asn264Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autoimmune lymphoproliferative syndrome (ALPS) (Invitae). 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 expected to disrupt FAS protein function. ClinVar contains an entry for this variant (Variation ID: 1505824).

#	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: Mar 5, 2024

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