rs764993670
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_177550.5(SLC13A5):c.1584A>G(p.Thr528=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 1 hom. )
Consequence
SLC13A5
NM_177550.5 synonymous
NM_177550.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.164
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 -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 17-6686330-T-C is Benign according to our data. Variant chr17-6686330-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 384178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.164 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000342 (50/1461818) while in subpopulation MID AF= 0.00312 (18/5766). AF 95% confidence interval is 0.00202. There are 1 homozygotes in gnomad4_exome. There are 30 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.1584A>G | p.Thr528= | synonymous_variant | 12/12 | ENST00000433363.7 | |
SLC13A5 | NM_001284509.2 | c.1533A>G | p.Thr511= | synonymous_variant | 12/12 | ||
SLC13A5 | NM_001284510.2 | c.1455A>G | p.Thr485= | synonymous_variant | 11/11 | ||
SLC13A5 | NM_001143838.3 | c.1446A>G | p.Thr482= | synonymous_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC13A5 | ENST00000433363.7 | c.1584A>G | p.Thr528= | synonymous_variant | 12/12 | 1 | NM_177550.5 | P1 | |
ENST00000634558.1 | n.511-3546T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249164Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134878
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461818Hom.: 1 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727218
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2017 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | SLC13A5: BP4, BP7 - |
Developmental and epileptic encephalopathy, 25 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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