NM_003060.4(SLC22A5):c.52del (p.Gln18fs) AND Renal carnitine transport defect

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 26, 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:: RCV000674681.4

Allele description [Variation Report for NM_003060.4(SLC22A5):c.52del (p.Gln18fs)]

NM_003060.4(SLC22A5):c.52del (p.Gln18fs)

Gene:

SLC22A5:solute carrier family 22 member 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_003060.4(SLC22A5):c.52del (p.Gln18fs)

HGVS:

NC_000005.10:g.132370024del
NG_008982.2:g.5321del
NM_001308122.2:c.52del
NM_003060.4:c.52delMANE SELECT
NP_001295051.1:p.Gln18fs
NP_003051.1:p.Gln18fs
NC_000005.9:g.131705715del
NC_000005.9:g.131705716del
NM_003060.3:c.52delC

Protein change:

Q18fs

Links:

dbSNP: rs1022453298

NCBI 1000 Genomes Browser:

rs1022453298

Molecular consequence:

NM_001308122.2:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003060.4:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Renal carnitine transport defect (CDSP)
Synonyms:: CARNITINE TRANSPORTER, PLASMA-MEMBRANE, DEFICIENCY OF; Primary carnitine deficiency; Carnitine uptake defect; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008919; MedGen: C0342788; Orphanet: 158; OMIM: 212140

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800063	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 21, 2018)	unknown	clinical testing	Citation Link,
SCV003211086	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9916797, 28492532
SCV004201288	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 26, 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

SCV000800063

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 21, 2018)

unknown

clinical testing

Citation Link,

SCV003211086

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004201288

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 26, 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

Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.

Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y, Koizumi A, Shoji Y, Takada G, Matsuishi T, Yoshino M, Kato H, Ohura T, Tsujimoto G, Hayakawa J, Shimane M, Tsuji A.

Nat Genet. 1999 Jan;21(1):91-4.

PubMed [citation]

PMID:: 9916797

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000800063.1

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

#	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

From Invitae, SCV003211086.2

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

Description

This sequence change creates a premature translational stop signal (p.Gln18Serfs*25) in the SLC22A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC22A5 are known to be pathogenic (PMID: 9916797). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 558416). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV004201288.1

#	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: Feb 20, 2024

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