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NM_015474.4(SAMHD1):c.1368T>G (p.Tyr456Ter) AND Aicardi-Goutieres syndrome 5

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 22, 2022
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:
RCV001051042.5

Allele description [Variation Report for NM_015474.4(SAMHD1):c.1368T>G (p.Tyr456Ter)]

NM_015474.4(SAMHD1):c.1368T>G (p.Tyr456Ter)

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.1368T>G (p.Tyr456Ter)
HGVS:
  • NC_000020.11:g.36905406A>C
  • NG_017059.1:g.51438T>G
  • NM_001363729.2:c.1368T>G
  • NM_001363733.2:c.1368T>G
  • NM_015474.4:c.1368T>GMANE SELECT
  • NP_001350658.1:p.Tyr456Ter
  • NP_001350662.1:p.Tyr456Ter
  • NP_056289.2:p.Tyr456Ter
  • LRG_281t1:c.1368T>G
  • LRG_281:g.51438T>G
  • NC_000020.10:g.35533809A>C
  • NM_015474.3:c.1368T>G
Protein change:
Y456*
Links:
dbSNP: rs769561543
NCBI 1000 Genomes Browser:
rs769561543
Molecular consequence:
  • NM_001363729.2:c.1368T>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001363733.2:c.1368T>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_015474.4:c.1368T>G - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001215175Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 22, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV001215175.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 847483). This variant has not been reported in the literature in individuals affected with SAMHD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr456*) 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024