ClinVar Genomic variation as it relates to human health
NM_003982.4(SLC7A7):c.625+1G>A
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003982.4(SLC7A7):c.625+1G>A
Variation ID: 56374 Accession: VCV000056374.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 22779925 (GRCh38) [ NCBI UCSC ] 14: 23249134 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 24, 2013 Jun 17, 2024 Mar 30, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_003982.4:c.625+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001126105.3:c.625+1G>A splice donor NM_001126106.4:c.625+1G>A splice donor NC_000014.9:g.22779925C>T NC_000014.8:g.23249134C>T NG_012851.2:g.54896G>A LRG_695:g.54896G>A LRG_695t1:c.625+1G>A LRG_695t2:c.625+1G>A LRG_695t3:c.625+1G>A - Protein change
- Other names
- IVS4DS, G-A, +1
- Canonical SPDI
- NC_000014.9:22779924:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
SLC7A7 | - | - |
GRCh38 GRCh37 |
747 | 812 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Mar 30, 2024 | RCV000049787.19 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 21, 2023 | RCV001547252.3 | |
SLC7A7-related disorder
|
Pathogenic (1) |
criteria provided, single submitter
|
Oct 19, 2022 | RCV003415815.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Nov 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002045733.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
Pathogenic
(May 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002803979.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Jul 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001766910.2
First in ClinVar: Aug 07, 2021 Last updated: Jul 29, 2023 |
Comment:
Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a … (more)
Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 31014432, 30630234, 10655553, 31905476, 23542076, 35964089, 37002123, 30961960, 35532875, 34134972, 34136918, 10737982, 29058386, 35669728, 10631139) (less)
|
|
Pathogenic
(Oct 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
SLC7A7-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004106114.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The SLC7A7 c.625+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant (also known as c.911+1G>A) was reported … (more)
The SLC7A7 c.625+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant (also known as c.911+1G>A) was reported in in the compound heterozygous and homozygous state in patients with Lysinuric protein intolerance. Functional studies also support this variant results in skipping of exon 4 (Dai et al. 2022. PubMed ID: 34134972; Mykkänen et al. 2000. PubMed ID: 10655553; Sperandeo et al. 2008. PubMed ID: 17764084). This variant is reported in 0.043% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-23249134-C-T). Variants that disrupt the consensus splice donor site in SLC7A7 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(Jan 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020725.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Mar 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004202511.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Sep 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001380501.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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). (less)
|
|
Pathogenic
(Jan 01, 2008)
|
no assertion criteria provided
Method: literature only
|
LYSINURIC PROTEIN INTOLERANCE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000026774.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 02, 2016 |
Comment on evidence:
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 … (more)
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. (less)
|
|
Pathogenic
(Aug 21, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002091189.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Lysinuric protein intolerance
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
de novo
|
Department of Traditional Chinese Medicine, Fujian Provincial Hospital
Accession: SCV002102511.1
First in ClinVar: Mar 08, 2022 Last updated: Mar 08, 2022 |
|
|
probable-pathogenic
(-)
|
no assertion criteria provided
Method: not provided
|
Lysinuric protein intolerance
Affected status: not provided
Allele origin:
not provided
|
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082194.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
|
Comment:
Converted during submission to Likely pathogenic.
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
New mutations in the SLC7A7 gene of two chinese sisters with lysinuric protein intolerance. | Zhang G | Pediatric pulmonology | 2017 | PMID: 29058386 |
Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. | Sperandeo MP | Human mutation | 2008 | PMID: 17764084 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families. | Noguchi A | Human mutation | 2000 | PMID: 10737982 |
Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI). | Mykkänen J | Human molecular genetics | 2000 | PMID: 10655553 |
Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. | Sperandeo MP | American journal of human genetics | 2000 | PMID: 10631139 |
Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. | Torrents D | The Journal of biological chemistry | 1998 | PMID: 9829974 |
Text-mined citations for rs386833822 ...
HelpRecord last updated Jun 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.