rs377289513
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_138773.4(SLC25A46):c.385-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,560,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_138773.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A46 | NM_138773.4 | c.385-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000355943.8 | |||
SLC25A46 | NM_001303249.3 | c.385-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
SLC25A46 | NM_001303250.3 | c.112-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
SLC25A46 | NR_138151.2 | n.498-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000355943.8 | c.385-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_138773.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000803 AC: 17AN: 211594Hom.: 0 AF XY: 0.0000605 AC XY: 7AN XY: 115684
GnomAD4 exome AF: 0.000126 AC: 178AN: 1407824Hom.: 0 Cov.: 27 AF XY: 0.000124 AC XY: 87AN XY: 701574
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74342
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2019 | The c.385-4A>G intronic variant results from an A to G substitution 4 nucleotides upstream from coding exon 4 in the SLC25A46 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Neuropathy, hereditary motor and sensory, type 6B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2023 | - - |
SLC25A46-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 07, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | SLC25A46: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at