2-227699279-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM2BP4_StrongBP6BS1
The NM_025243.4(SLC19A3):c.436G>A(p.Val146Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_025243.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152174Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251210Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135784
GnomAD4 exome AF: 0.0000848 AC: 124AN: 1461778Hom.: 0 Cov.: 33 AF XY: 0.0000866 AC XY: 63AN XY: 727180
GnomAD4 genome AF: 0.000381 AC: 58AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:2
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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 -
SLC19A3-related disorder Uncertain:1
The SLC19A3 c.436G>A variant is predicted to result in the amino acid substitution p.Val146Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of African descent in gnomAD, including one homozygote. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Biotin-responsive basal ganglia disease Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at