NM_014252.4(SLC25A15):c.554_557del (p.Phe185fs) AND Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome

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

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 23, 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:: RCV001783757.5

Allele description

NM_014252.4(SLC25A15):c.554_557del (p.Phe185fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q14.11

Genomic location:

Preferred name:

NM_014252.4(SLC25A15):c.554_557del (p.Phe185fs)

HGVS:

NC_000013.11:g.40807395_40807398del
NG_012248.1:g.22985_22988del
NM_014252.4:c.554_557delMANE SELECT
NP_055067.1:p.Phe185fs
NC_000013.10:g.41381529_41381532del
NC_000013.10:g.41381531_41381534del
NM_014252.3:c.554_557del

Protein change:

F185fs

Links:

dbSNP: rs1882233400

NCBI 1000 Genomes Browser:

rs1882233400

Molecular consequence:

NM_014252.4:c.554_557del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Burkholderia gladioli strain AU29541, whole genome shotgun sequencing project
Burkholderia gladioli strain AU29541, whole genome shotgun sequencing project
gi|1356431552|gb|PVHE00000000.1|PVH 0000

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002023532	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 25, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004385502	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11552031, 19242930, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002023532

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 25, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004385502

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 23, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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

See all PubMed Citations (4)

Details of each submission

From Revvity Omics, Revvity, SCV002023532.3

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004385502.1

#	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. 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: 1325080). 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.Phe185Serfs*8) 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

Last Updated: Mar 16, 2024

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