NM_003982.4(SLC7A7):c.625+1G>A AND Lysinuric protein intolerance

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

Germline classification:: Pathogenic (9 submissions)
Last evaluated:: Mar 30, 2024
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:: RCV000049787.19

Allele description

NM_003982.4(SLC7A7):c.625+1G>A

Gene:

SLC7A7:solute carrier family 7 member 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_003982.4(SLC7A7):c.625+1G>A

HGVS:

NC_000014.9:g.22779925C>T
NG_012851.2:g.54896G>A
NM_001126105.3:c.625+1G>A
NM_001126106.4:c.625+1G>A
NM_003982.4:c.625+1G>AMANE SELECT
LRG_695t1:c.625+1G>A
LRG_695t2:c.625+1G>A
LRG_695t3:c.625+1G>A
LRG_695:g.54896G>A
NC_000014.8:g.23249134C>T
NM_001126105.2:c.625+1G>A
NM_001126106.2:c.625+1G>A
NM_001126106.4:c.625+1G>A

Nucleotide change:

IVS4DS, G-A, +1

Links:

OMIM: 603593.0009; dbSNP: rs386833822

NCBI 1000 Genomes Browser:

rs386833822

Molecular consequence:

NM_001126105.3:c.625+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126106.4:c.625+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003982.4:c.625+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Lysinuric protein intolerance (LPI)
Synonyms:: Dibasicamino aciduria II
Identifiers:: MONDO: MONDO:0009109; MedGen: C0268647; Orphanet: 470; OMIM: 222700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026774	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10737982, 17764084
SCV000082194	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (2) [See all records that cite these PMIDs] 10655553, 10737982
SCV001380501	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 17764084, 10631139, 29058386, 28492532
SCV002020725	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 22, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002045733	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002091189	Natera, Inc.	no assertion criteria provided	Pathogenic (Aug 21, 2020)	germline	clinical testing
SCV002102511	Department of Traditional Chinese Medicine, Fujian Provincial Hospital	no assertion criteria provided	Pathogenic	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV002803979	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 25, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004202511	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000082194

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	unknown	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Mykkänen J, Torrents D, Pineda M, Camps M, Yoldi ME, Horelli-Kuitunen N, Huoponen K, Heinonen M, Oksanen J, Simell O, Savontaus ML, Zorzano A, Palacín M, Aula P.

Hum Mol Genet. 2000 Feb 12;9(3):431-8.

PubMed [citation]

PMID:: 10655553

SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families.

Noguchi A, Shoji Y, Koizumi A, Takahashi T, Matsumori M, Kayo T, Ohata T, Wada Y, Yoshimura I, Maisawa S, Konishi M, Takasago Y, Takada G.

Hum Mutat. 2000;15(4):367-72.

PubMed [citation]

PMID:: 10737982

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000026774.3

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

Description

For discussion of the splice site mutation in the SLC7A7 gene that was found in compound heterozygous state in 2 children with lysinuric protein intolerance (LPI; 222700) by Noguchi et al. (2000), see 603593.0008. The authors cited this mutation as 911+1G-A.

Sperandeo et al. (2008) noted that this mutation corresponds to 625+1G-A in intron 4 of the SLC7A7 gene in the current nomenclature system and results in the skipping of exon 4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082194.1

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

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001380501.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

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 sequence change affects a donor splice site in intron 4 of the SLC7A7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC7A7 are known to be pathogenic (PMID: 10631139, 17764084). This variant is present in population databases (rs386833822, gnomAD 0.05%). Disruption of this splice site has been observed in individuals with lysinuric protein intolerance (PMID: 10631139, 29058386). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS3+1G>A or IVS4+1C>T. ClinVar contains an entry for this variant (Variation ID: 56374).

#	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 Revvity Omics, Revvity, SCV002020725.3

#	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 Genome-Nilou Lab, SCV002045733.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002091189.1

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

From Department of Traditional Chinese Medicine, Fujian Provincial Hospital, SCV002102511.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002803979.1

#	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

From Baylor Genetics, SCV004202511.2

#	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: Jun 23, 2024

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