chr17-6686286-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_177550.5(SLC13A5):c.1628C>A(p.Ala543Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,066 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A543S) has been classified as Uncertain significance.
Frequency
Consequence
NM_177550.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC13A5 | NM_177550.5 | c.1628C>A | p.Ala543Asp | missense_variant | 12/12 | ENST00000433363.7 | |
SLC13A5 | NM_001284509.2 | c.1577C>A | p.Ala526Asp | missense_variant | 12/12 | ||
SLC13A5 | NM_001284510.2 | c.1499C>A | p.Ala500Asp | missense_variant | 11/11 | ||
SLC13A5 | NM_001143838.3 | c.1490C>A | p.Ala497Asp | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC13A5 | ENST00000433363.7 | c.1628C>A | p.Ala543Asp | missense_variant | 12/12 | 1 | NM_177550.5 | P1 | |
ENST00000634558.1 | n.511-3590G>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250302Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135388
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727238
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 25 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 01, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 543 of the SLC13A5 protein (p.Ala543Asp). This variant is present in population databases (rs202208840, gnomAD 0.03%). 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: 541967). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at