NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 1, 2021
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:
RCV001851363.4

Allele description [Variation Report for NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln)]

NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln)

Gene:
SGPL1:sphingosine-1-phosphate lyase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln)
HGVS:
  • NC_000010.11:g.70868394G>A
  • NM_003901.4:c.665G>AMANE SELECT
  • NP_003892.2:p.Arg222Gln
  • NC_000010.10:g.72628151G>A
  • NM_003901.3:c.665G>A
Protein change:
R222Q; ARG222GLN
Links:
OMIM: 603729.0001; dbSNP: rs769259446
NCBI 1000 Genomes Browser:
rs769259446
Molecular consequence:
  • NM_003901.4:c.665G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002152961Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 1, 2021)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency.

Settas N, Persky R, Faucz FR, Sheanon N, Voutetakis A, Lodish M, Metherell LA, Stratakis CA.

J Clin Endocrinol Metab. 2019 May 1;104(5):1484-1490. doi: 10.1210/jc.2018-02238.

PubMed [citation]
PMID:
30517686
PMCID:
PMC6435096

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.

Monies D, Abouelhoda M, Assoum M, Moghrabi N, Rafiullah R, Almontashiri N, Alowain M, Alzaidan H, Alsayed M, Subhani S, Cupler E, Faden M, Alhashem A, Qari A, Chedrawi A, Aldhalaan H, Kurdi W, Khan S, Rahbeeni Z, Alotaibi M, Goljan E, Elbardisy H, et al.

Am J Hum Genet. 2019 Jun 6;104(6):1182-1201. doi: 10.1016/j.ajhg.2019.04.011. Epub 2019 May 23. Erratum in: Am J Hum Genet. 2019 Oct 3;105(4):879.

PubMed [citation]
PMID:
31130284
PMCID:
PMC6562004
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002152961.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 430861). This variant has been observed in individual(s) with clinical features of SGPL1-related conditions (PMID: 28165343, 30517686, 31130284). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs769259446, ExAC 0.006%). This sequence change replaces arginine with glutamine at codon 222 of the SGPL1 protein (p.Arg222Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg222 amino acid residue in SGPL1. Other variant(s) that disrupt this residue have been observed in individuals with SGPL1-related conditions (PMID: 28165339), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this variant affects SGPL1 protein function (PMID: 28165343).

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

Last Updated: May 19, 2024