rs138839321
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_025243.4(SLC19A3):c.1370G>A(p.Ser457Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000188 in 1,614,076 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S457K) has been classified as Uncertain significance.
Frequency
Consequence
NM_025243.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC19A3 | NM_025243.4 | c.1370G>A | p.Ser457Asn | missense_variant | 6/6 | ENST00000644224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC19A3 | ENST00000644224.2 | c.1370G>A | p.Ser457Asn | missense_variant | 6/6 | NM_025243.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000422 AC: 106AN: 251268Hom.: 0 AF XY: 0.000442 AC XY: 60AN XY: 135828
GnomAD4 exome AF: 0.000185 AC: 270AN: 1461798Hom.: 1 Cov.: 31 AF XY: 0.000209 AC XY: 152AN XY: 727206
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2021 | The c.1370G>A (p.S457N) alteration is located in exon 6 (coding exon 5) of the SLC19A3 gene. This alteration results from a G to A substitution at nucleotide position 1370, causing the serine (S) at amino acid position 457 to be replaced by an asparagine (N). The p.S457N alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Biotin-responsive basal ganglia disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at