NM_015474.4(SAMHD1):c.580C>T (p.Arg194Ter) AND Aicardi-Goutieres syndrome 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 7, 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:: RCV001067942.6

Allele description [Variation Report for NM_015474.4(SAMHD1):c.580C>T (p.Arg194Ter)]

NM_015474.4(SAMHD1):c.580C>T (p.Arg194Ter)

Gene:

SAMHD1:SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.23

Genomic location:

Preferred name:

NM_015474.4(SAMHD1):c.580C>T (p.Arg194Ter)

HGVS:

NC_000020.11:g.36930805G>A
NG_017059.1:g.26039C>T
NM_001363729.2:c.580C>T
NM_001363733.2:c.580C>T
NM_015474.4:c.580C>TMANE SELECT
NP_001350658.1:p.Arg194Ter
NP_001350662.1:p.Arg194Ter
NP_056289.2:p.Arg194Ter
LRG_281t1:c.580C>T
LRG_281:g.26039C>T
NC_000020.10:g.35559208G>A
NM_015474.3:c.580C>T

Protein change:

R194*

Links:

dbSNP: rs1300333132

NCBI 1000 Genomes Browser:

rs1300333132

Molecular consequence:

NM_001363729.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363733.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015474.4:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Aicardi-Goutieres syndrome 5
Identifiers:: MONDO: MONDO:0013059; MedGen: C2749659; Orphanet: 51; OMIM: 612952

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001233027	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19525956, 22461318, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001233027

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 7, 2023)

germline

clinical testing

PubMed (3)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, Ali M, Gornall H, Couthard LR, Aeby A, Attard-Montalto SP, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, et al.

Nat Genet. 2009 Jul;41(7):829-32. doi: 10.1038/ng.373. Epub 2009 Jun 14.

PubMed [citation]

PMID:: 19525956
PMCID:: PMC4154505

SAMHD1 is a nucleic-acid binding protein that is mislocalized due to aicardi-goutières syndrome-associated mutations.

Goncalves A, Karayel E, Rice GI, Bennett KL, Crow YJ, Superti-Furga G, Bürckstümmer T.

Hum Mutat. 2012 Jul;33(7):1116-22. doi: 10.1002/humu.22087. Epub 2012 Apr 16.

PubMed [citation]

PMID:: 22461318

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001233027.5

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

Description

This variant has not been reported in the literature in individuals affected with SAMHD1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg194*) in the SAMHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SAMHD1 are known to be pathogenic (PMID: 19525956, 22461318). ClinVar contains an entry for this variant (Variation ID: 861422). 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

Last Updated: Sep 29, 2024

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