rs1809352
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001126121.2(SLC25A19):c.*2T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 1,613,434 control chromosomes in the GnomAD database, including 685,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.88 ( 59952 hom., cov: 36)
Exomes 𝑓: 0.92 ( 625901 hom. )
Consequence
SLC25A19
NM_001126121.2 3_prime_UTR
NM_001126121.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.842
Genes affected
SLC25A19 (HGNC:14409): (solute carrier family 25 member 19) This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 17-75273449-A-G is Benign according to our data. Variant chr17-75273449-A-G is described in ClinVar as [Benign]. Clinvar id is 130327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75273449-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A19 | NM_001126121.2 | c.*2T>C | 3_prime_UTR_variant | 8/8 | ENST00000416858.7 | ||
MIF4GD-DT | NR_036520.1 | n.2151A>G | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A19 | ENST00000416858.7 | c.*2T>C | 3_prime_UTR_variant | 8/8 | 1 | NM_001126121.2 | P1 | ||
MIF4GD-DT | ENST00000585075.1 | n.2081A>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.884 AC: 134581AN: 152212Hom.: 59922 Cov.: 36
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GnomAD3 exomes AF: 0.930 AC: 231799AN: 249178Hom.: 108135 AF XY: 0.934 AC XY: 125981AN XY: 134840
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GnomAD4 exome AF: 0.925 AC: 1351340AN: 1461104Hom.: 625901 Cov.: 49 AF XY: 0.927 AC XY: 673655AN XY: 726828
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GnomAD4 genome ? AF: 0.884 AC: 134663AN: 152330Hom.: 59952 Cov.: 36 AF XY: 0.889 AC XY: 66212AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 11, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 15, 2013 | - - |
Amish lethal microcephaly Benign:2
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Progressive demyelinating neuropathy with bilateral striatal necrosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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Name
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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