NM_015474.4(SAMHD1):c.541G>A (p.Ala181Thr) AND Aicardi-Goutieres syndrome 5

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 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:: RCV000810117.4

Allele description

NM_015474.4(SAMHD1):c.541G>A (p.Ala181Thr)

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.541G>A (p.Ala181Thr)

HGVS:

NC_000020.11:g.36930844C>T
NG_017059.1:g.26000G>A
NM_001363729.2:c.541G>A
NM_001363733.2:c.541G>A
NM_015474.4:c.541G>AMANE SELECT
NP_001350658.1:p.Ala181Thr
NP_001350662.1:p.Ala181Thr
NP_056289.2:p.Ala181Thr
NP_056289.2:p.Ala181Thr
LRG_281t1:c.541G>A
LRG_281:g.26000G>A
LRG_281p1:p.Ala181Thr
NC_000020.10:g.35559247C>T
NM_015474.3:c.541G>A

Protein change:

A181T

Links:

dbSNP: rs1455837248

NCBI 1000 Genomes Browser:

rs1455837248

Molecular consequence:

NM_001363729.2:c.541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363733.2:c.541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015474.4:c.541G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000950306	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	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

SCV000950306

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

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, SCV000950306.4

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 181 of the SAMHD1 protein (p.Ala181Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SAMHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 654205). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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: Feb 7, 2023

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