NM_014252.4(SLC25A15):c.236C>G (p.Ser79Ter) AND Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 15, 2023
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:: RCV001898279.5

Allele description [Variation Report for NM_014252.4(SLC25A15):c.236C>G (p.Ser79Ter)]

NM_014252.4(SLC25A15):c.236C>G (p.Ser79Ter)

Gene:

SLC25A15:solute carrier family 25 member 15 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.11

Genomic location:

Preferred name:

NM_014252.4(SLC25A15):c.236C>G (p.Ser79Ter)

HGVS:

NC_000013.11:g.40799237C>G
NG_012248.1:g.14827C>G
NM_014252.4:c.236C>GMANE SELECT
NP_055067.1:p.Ser79Ter
NC_000013.10:g.41373373C>G
NR_038258.1:n.2110G>C
NR_038259.1:n.1939G>C

Protein change:

S79*

Links:

dbSNP: rs2138045987

NCBI 1000 Genomes Browser:

rs2138045987

Molecular consequence:

NR_038258.1:n.2110G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_038259.1:n.1939G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_014252.4:c.236C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS)
Synonyms:: Ornithine translocase deficiency syndrome; HHH syndrome; Ornithine translocase deficiency
Identifiers:: MONDO: MONDO:0009393; MedGen: C0268540; Orphanet: 415; OMIM: 238970

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002166199	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11552031, 19242930, 28492532
SCV004201686	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 15, 2023)	unknown	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

SCV002166199

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 25, 2022)

germline

clinical testing

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

SCV004201686

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 15, 2023)

unknown

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

Salvi S, Santorelli FM, Bertini E, Boldrini R, Meli C, Donati A, Burlina AB, Rizzo C, Di Capua M, Fariello G, Dionisi-Vici C.

Neurology. 2001 Sep 11;57(5):911-4.

PubMed [citation]

PMID:: 11552031

Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study.

Tessa A, Fiermonte G, Dionisi-Vici C, Paradies E, Baumgartner MR, Chien YH, Loguercio C, de Baulny HO, Nassogne MC, Schiff M, Deodato F, Parenti G, Rutledge SL, Vilaseca MA, Melone MA, Scarano G, Aldamiz-Echevarría L, Besley G, Walter J, Martinez-Hernandez E, Hernandez JM, Pierri CL, et al.

Hum Mutat. 2009 May;30(5):741-8. doi: 10.1002/humu.20930.

PubMed [citation]

PMID:: 19242930

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002166199.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1393388). This variant has not been reported in the literature in individuals affected with SLC25A15-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser79*) in the SLC25A15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A15 are known to be pathogenic (PMID: 11552031, 19242930).

#	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

From Baylor Genetics, SCV004201686.1

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

#	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

Last Updated: Sep 29, 2024

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