NM_005629.4(SLC6A8):c.1289_1290del (p.Leu430fs) AND Creatine transporter deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 2023
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:: RCV003512956.2

Allele description [Variation Report for NM_005629.4(SLC6A8):c.1289_1290del (p.Leu430fs)]

NM_005629.4(SLC6A8):c.1289_1290del (p.Leu430fs)

Gene:

SLC6A8:solute carrier family 6 member 8 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_005629.4(SLC6A8):c.1289_1290del (p.Leu430fs)

HGVS:

NC_000023.11:g.153694164_153694165del
NG_012016.2:g.10868_10869del
NM_001142805.2:c.1259_1260del
NM_001142806.1:c.944_945del
NM_005629.4:c.1289_1290delMANE SELECT
NP_001136277.1:p.Leu420fs
NP_001136278.1:p.Leu315fs
NP_005620.1:p.Leu430fs
NC_000023.10:g.152959618_152959619del
NC_000023.10:g.152959619_152959620del

Protein change:

L315fs

Molecular consequence:

NM_001142805.2:c.1259_1260del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142806.1:c.944_945del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005629.4:c.1289_1290del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Creatine transporter deficiency (CCDS1)
Synonyms:: Creatine deficiency, X-linked; Mental retardation , X-linked with seizures, short stature and midface hypoplasia; Mental retardation , X-linked, with creatine transport deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010305; MedGen: C1845862; Orphanet: 52503; OMIM: 300352

Recent activity

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Homo sapiens tumor necrosis factor, alpha-induced protein 8-like 1 (TNFAIP8L1), ...
Homo sapiens tumor necrosis factor, alpha-induced protein 8-like 1 (TNFAIP8L1), mRNA
gi|22748780|ref|NM_152362.1|

Nucleotide
Homo sapiens pleckstrin homology domain interacting protein (PHIP), RefSeqGene o...
Homo sapiens pleckstrin homology domain interacting protein (PHIP), RefSeqGene on chromosome 6
gi|1084352549|ref|NG_051932.1|

Nucleotide
cerebral protein-5 [Homo sapiens]
cerebral protein-5 [Homo sapiens]
gi|13874427|dbj|BAB46920.1|

Protein
Pgant1 [Ceratitis capitata]
Pgant1 [Ceratitis capitata]
Gene ID:101462694

Gene
GCNT4 [Alligator mississippiensis]
GCNT4 [Alligator mississippiensis]
Gene ID:106737261

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004260741	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22281021, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004260741

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2023)

germline

clinical testing

PubMed (2)
[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

Detection of variants in SLC6A8 and functional analysis of unclassified missense variants.

Betsalel OT, Pop A, Rosenberg EH, Fernandez-Ojeda M; Creatine Transporter Research, Group., Jakobs C, Salomons GS.

Mol Genet Metab. 2012 Apr;105(4):596-601. doi: 10.1016/j.ymgme.2011.12.022. Epub 2012 Jan 6.

PubMed [citation]

PMID:: 22281021

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004260741.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. This variant has not been reported in the literature in individuals affected with SLC6A8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu430Argfs*34) in the SLC6A8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC6A8 are known to be pathogenic (PMID: 22281021).

#	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: Sep 29, 2024

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