chr1-108136838-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP3_Moderate
The NM_013386.5(SLC25A24):c.1250-1G>A variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,602,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013386.5 splice_acceptor
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A24 | NM_013386.5 | c.1250-1G>A | splice_acceptor_variant | ENST00000565488.6 | |||
SLC25A24 | NM_213651.3 | c.1193-1G>A | splice_acceptor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A24 | ENST00000565488.6 | c.1250-1G>A | splice_acceptor_variant | 1 | NM_013386.5 | P1 | |||
SLC25A24 | ENST00000370041.4 | c.1193-1G>A | splice_acceptor_variant | 1 | |||||
SLC25A24 | ENST00000264128.13 | c.*829-1G>A | splice_acceptor_variant, NMD_transcript_variant | 5 | |||||
SLC25A24 | ENST00000648874.1 | c.*571-1G>A | splice_acceptor_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151504Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1450710Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 721472
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151504Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 73924
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1511499). This variant has not been reported in the literature in individuals affected with SLC25A24-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 of the SLC25A24 gene. It does not directly change the encoded amino acid sequence of the SLC25A24 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at