chr17-6686216-AAT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM4BS1_Supporting
The NM_177550.5(SLC13A5):βc.1696_1697delβ(p.Ile566Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,008 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.00032 ( 1 hom., cov: 32)
Exomes π: 0.000016 ( 0 hom. )
Consequence
SLC13A5
NM_177550.5 frameshift
NM_177550.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.457
Genes affected
SLC13A5 (HGNC:23089): (solute carrier family 13 member 5) This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 610 codons.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000315 (48/152148) while in subpopulation AMR AF= 0.00314 (48/15284). AF 95% confidence interval is 0.00243. There are 1 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.1696_1697del | p.Ile566Ter | frameshift_variant | 12/12 | ENST00000433363.7 | |
SLC13A5 | NM_001143838.3 | c.1558_1559del | p.Ile520Ter | frameshift_variant | 11/11 | ||
SLC13A5 | NM_001284509.2 | c.1645_1646del | p.Ile549Ter | frameshift_variant | 12/12 | ||
SLC13A5 | NM_001284510.2 | c.1567_1568del | p.Ile523Ter | frameshift_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC13A5 | ENST00000433363.7 | c.1696_1697del | p.Ile566Ter | frameshift_variant | 12/12 | 1 | NM_177550.5 | P1 | |
ENST00000634558.1 | n.511-3657_511-3656del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000315 AC: 48AN: 152148Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000103 AC: 26AN: 251388Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135864
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461860Hom.: 0 AF XY: 0.00000825 AC XY: 6AN XY: 727238
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GnomAD4 genome AF: 0.000315 AC: 48AN: 152148Hom.: 1 Cov.: 32 AF XY: 0.000471 AC XY: 35AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 17, 2023 | PVS1_moderate - |
Developmental and epileptic encephalopathy, 25 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 13, 2022 | This sequence change creates a premature translational stop signal (p.Ile566*) in the SLC13A5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the SLC13A5 protein. This variant is present in population databases (no rsID available, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SLC13A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 660015). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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