rs796262035
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1
The NM_000341.4(SLC3A1):c.1136+3del variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,613,908 control chromosomes in the GnomAD database, including 9,573 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.14 ( 1770 hom., cov: 30)
Exomes 𝑓: 0.096 ( 7803 hom. )
Consequence
SLC3A1
NM_000341.4 splice_donor
NM_000341.4 splice_donor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.060252674 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.5, offset of 0 (no position change), new splice context is: cagGTgacc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
BP6
?
Variant 2-44301128-GT-G is Benign according to our data. Variant chr2-44301128-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 336199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-44301128-GT-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC3A1 | NM_000341.4 | c.1136+3del | splice_donor_variant | ENST00000260649.11 | |||
SLC3A1 | XM_011533047.4 | c.1136+3del | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC3A1 | ENST00000260649.11 | c.1136+3del | splice_donor_variant | 1 | NM_000341.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.136 AC: 20672AN: 152022Hom.: 1763 Cov.: 30
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GnomAD3 exomes AF: 0.0875 AC: 21977AN: 251244Hom.: 1336 AF XY: 0.0830 AC XY: 11268AN XY: 135822
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GnomAD4 exome AF: 0.0962 AC: 140568AN: 1461768Hom.: 7803 Cov.: 30 AF XY: 0.0936 AC XY: 68053AN XY: 727188
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GnomAD4 genome ? AF: 0.136 AC: 20715AN: 152140Hom.: 1770 Cov.: 30 AF XY: 0.134 AC XY: 9944AN XY: 74374
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cystinuria Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 242/2178=11.1% - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2020 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at