rs17853011
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_025243.4(SLC19A3):āc.99A>Gā(p.Pro33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,948 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 2 hom. )
Consequence
SLC19A3
NM_025243.4 synonymous
NM_025243.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.686
Genes affected
SLC19A3 (HGNC:16266): (solute carrier family 19 member 3) This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild cognitive disability, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 2-227702220-T-C is Benign according to our data. Variant chr2-227702220-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 334883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.686 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC19A3 | NM_025243.4 | c.99A>G | p.Pro33= | synonymous_variant | 2/6 | ENST00000644224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC19A3 | ENST00000644224.2 | c.99A>G | p.Pro33= | synonymous_variant | 2/6 | NM_025243.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000549 AC: 138AN: 251440Hom.: 2 AF XY: 0.000552 AC XY: 75AN XY: 135892
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GnomAD4 exome AF: 0.000109 AC: 160AN: 1461676Hom.: 2 Cov.: 30 AF XY: 0.000107 AC XY: 78AN XY: 727164
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Biotin-responsive basal ganglia disease Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at