rs61520357
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_177550.5(SLC13A5):c.1101A>G(p.Leu367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,684 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0085 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00086 ( 14 hom. )
Consequence
SLC13A5
NM_177550.5 synonymous
NM_177550.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.27
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 17-6694152-T-C is Benign according to our data. Variant chr17-6694152-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 380942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.27 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00845 (1287/152268) while in subpopulation AFR AF= 0.0294 (1220/41558). AF 95% confidence interval is 0.028. There are 21 homozygotes in gnomad4. There are 573 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.1101A>G | p.Leu367= | synonymous_variant | 8/12 | ENST00000433363.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC13A5 | ENST00000433363.7 | c.1101A>G | p.Leu367= | synonymous_variant | 8/12 | 1 | NM_177550.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00847 AC: 1288AN: 152150Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00205 AC: 514AN: 250402Hom.: 3 AF XY: 0.00161 AC XY: 218AN XY: 135452
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GnomAD4 exome AF: 0.000862 AC: 1260AN: 1461416Hom.: 14 Cov.: 30 AF XY: 0.000730 AC XY: 531AN XY: 726980
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GnomAD4 genome ? AF: 0.00845 AC: 1287AN: 152268Hom.: 21 Cov.: 32 AF XY: 0.00770 AC XY: 573AN XY: 74456
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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
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 23, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Developmental and epileptic encephalopathy, 25 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at