chr3-48862536-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000387.6(SLC25A20):c.535+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,598,344 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 3 hom. )
Consequence
SLC25A20
NM_000387.6 splice_donor_region, intron
NM_000387.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001004
2
Clinical Significance
Conservation
PhyloP100: 0.0950
Genes affected
SLC25A20 (HGNC:1421): (solute carrier family 25 member 20) This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 3-48862536-G-A is Benign according to our data. Variant chr3-48862536-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 529871.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}. Variant chr3-48862536-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000242 (350/1446020) while in subpopulation MID AF= 0.00724 (41/5662). AF 95% confidence interval is 0.00549. There are 3 homozygotes in gnomad4_exome. There are 174 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A20 | NM_000387.6 | c.535+6C>T | splice_donor_region_variant, intron_variant | ENST00000319017.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A20 | ENST00000319017.5 | c.535+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_000387.6 | P1 | |||
SLC25A20 | ENST00000430379.5 | c.316+6C>T | splice_donor_region_variant, intron_variant | 3 | |||||
SLC25A20 | ENST00000440964.1 | c.*365+6C>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152206Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000374 AC: 94AN: 251416Hom.: 2 AF XY: 0.000353 AC XY: 48AN XY: 135896
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GnomAD4 exome AF: 0.000242 AC: 350AN: 1446020Hom.: 3 Cov.: 28 AF XY: 0.000242 AC XY: 174AN XY: 720470
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GnomAD4 genome AF: 0.000295 AC: 45AN: 152324Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74484
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Carnitine acylcarnitine translocase deficiency Uncertain:1Benign:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 23, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at