NM_000043.6(FAS):c.748C>T (p.Arg250Ter) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Sep 10, 2022
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:: RCV000988433.5

Allele description [Variation Report for NM_000043.6(FAS):c.748C>T (p.Arg250Ter)]

NM_000043.6(FAS):c.748C>T (p.Arg250Ter)

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.748C>T (p.Arg250Ter)

HGVS:

NC_000010.11:g.89014190C>T
NG_009089.2:g.28660C>T
NM_000043.6:c.748C>TMANE SELECT
NM_001320619.2:c.*71C>T
NM_152871.4:c.685C>T
NM_152872.4:c.*60C>T
NP_000034.1:p.Arg250Ter
NP_690610.1:p.Arg229Ter
LRG_134t1:c.748C>T
LRG_134:g.28660C>T
NC_000010.10:g.90773947C>T
NM_000043.4:c.748C>T
NR_028033.4:n.655C>T
NR_028034.4:n.517C>T
NR_028035.4:n.580C>T
NR_028036.4:n.718C>T
NR_135313.2:n.635C>T
NR_135314.2:n.914C>T
NR_135315.2:n.667C>T

Protein change:

R229*

Links:

dbSNP: rs778993919

NCBI 1000 Genomes Browser:

rs778993919

Molecular consequence:

NM_001320619.2:c.*71C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152872.4:c.*60C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NR_028033.4:n.655C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028034.4:n.517C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028035.4:n.580C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028036.4:n.718C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135313.2:n.635C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135314.2:n.914C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135315.2:n.667C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000043.6:c.748C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_152871.4:c.685C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001138149	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002073912	Genomics Facility, Ludwig-Maximilians-Universität München	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 11, 2022)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 27789675
SCV003439552	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18948840, 21490157, 32499645, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001138149

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002073912

Genomics Facility, Ludwig-Maximilians-Universität München

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 11, 2022)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003439552

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 10, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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

Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome.

Klemann C, Esquivel M, Magerus-Chatinet A, Lorenz MR, Fuchs I, Neveux N, Castelle M, Rohr J, da Cunha CB, Ebinger M, Kobbe R, Kremens B, Kollert F, Gambineri E, Lehmberg K, Seidel MG, Siepermann K, Voelker T, Schuster V, Goldacker S, Schwarz K, Speckmann C, et al.

Haematologica. 2017 Feb;102(2):e52-e56. doi: 10.3324/haematol.2016.153411. Epub 2016 Oct 27. No abstract available.

PubMed [citation]

PMID:: 27789675
PMCID:: PMC5286954

See all PubMed Citations (6)

Details of each submission

From Mendelics, SCV001138149.1

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

#	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 Genomics Facility, Ludwig-Maximilians-Universität München, SCV002073912.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	PBMCs	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003439552.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg250*) in the FAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 86 amino acid(s) of the FAS protein. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 802620). This variant is also known as p.R348X. This premature translational stop signal has been observed in individual(s) with autoimmune lymphoproliferative syndrome and/or clinical features of FAS-related conditions (PMID: 18948840, 21490157, 32499645). This variant is not present in population databases (gnomAD no frequency).

#	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: Apr 15, 2024

ClinVar

Relating variation to medicine