chr5-132370103-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4
The NM_003060.4(SLC22A5):āc.131C>Gā(p.Ala44Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A44V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003060.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.131C>G | p.Ala44Gly | missense_variant | 1/10 | ENST00000245407.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.131C>G | p.Ala44Gly | missense_variant | 1/10 | 1 | NM_003060.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459836Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726252
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Renal carnitine transport defect Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 02, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 44 of the SLC22A5 protein (p.Ala44Gly). This variant is present in population databases (rs199689597, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC22A5 protein function. This variant disrupts the p.Ala44 amino acid residue in SLC22A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23963628, 28711408, 28841266; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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