NM_003982.4(SLC7A7):c.894+1G>T AND Lysinuric protein intolerance

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 14, 2022
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:: RCV000049793.7

Allele description [Variation Report for NM_003982.4(SLC7A7):c.894+1G>T]

NM_003982.4(SLC7A7):c.894+1G>T

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.894+1G>T

HGVS:

NC_000014.9:g.22776194C>A
NG_012851.2:g.58627G>T
NM_001126105.3:c.894+1G>T
NM_001126106.4:c.894+1G>T
NM_003982.4:c.894+1G>TMANE SELECT
LRG_695t1:c.894+1G>T
LRG_695t2:c.894+1G>T
LRG_695t3:c.894+1G>T
LRG_695:g.58627G>T
NC_000014.8:g.23245403C>A
NM_001126105.2:c.894+1G>T
NM_001126106.2:c.894+1G>T

Links:

dbSNP: rs386833827

NCBI 1000 Genomes Browser:

rs386833827

Molecular consequence:

NM_001126105.3:c.894+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126106.4:c.894+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003982.4:c.894+1G>T - 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
SCV000082200	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV001581671	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 24, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 10631139, 17764084, 28492532
SCV002795575	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 14, 2022)	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

SCV000082200

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

no assertion criteria provided

probable-pathogenic

not provided

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

SCV001581671

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 24, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002795575

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 14, 2022)

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: SCV000082200

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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Sperandeo MP, Bassi MT, Riboni M, Parenti G, Buoninconti A, Manzoni M, Incerti B, Larocca MR, Di Rocco M, Strisciuglio P, Dianzani I, Parini R, Candito M, Endo F, Ballabio A, Andria G, Sebastio G, Borsani G.

Am J Hum Genet. 2000 Jan;66(1):92-9.

PubMed [citation]

PMID:: 10631139
PMCID:: PMC1288352

See all PubMed Citations (5)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082200.1

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001581671.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects a donor splice site in intron 6 of the SLC7A7 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with lysinuric protein intolerance (PMID: 10631139). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS6+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 56380). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). 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 Fulgent Genetics, Fulgent Genetics, SCV002795575.1

#	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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