NM_177550.5:c.1654T>A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_177550.5(SLC13A5):c.1654T>A(p.Phe552Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_177550.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.1654T>A | p.Phe552Ile | missense_variant | Exon 12 of 12 | ENST00000433363.7 | NP_808218.1 | |
SLC13A5 | NM_001284509.2 | c.1603T>A | p.Phe535Ile | missense_variant | Exon 12 of 12 | NP_001271438.1 | ||
SLC13A5 | NM_001284510.2 | c.1525T>A | p.Phe509Ile | missense_variant | Exon 11 of 11 | NP_001271439.1 | ||
SLC13A5 | NM_001143838.3 | c.1516T>A | p.Phe506Ile | missense_variant | Exon 11 of 11 | NP_001137310.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250970Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135702
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 25 Uncertain:3
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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
The p.Phe552Ile variant in SLC13A5 has been reported in 1 homozygous individual with developmental and epileptic encephalopathy (PMID: 31054490) and has been identified in 0.005% (1/18394) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1453393447). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 1030354) and has been interpreted as VUS by Baylor Genetics. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Phe552Ile variant is uncertain. ACMG/AMP Criteria applied: PM3_supporting, PM2_supporting (Richards 2015). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at