5-110738249-T-G
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001303250.3(SLC25A46):c.10+2T>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000882 in 1,134,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 8.8e-7 ( 0 hom. )
Consequence
SLC25A46
NM_001303250.3 splice_donor, intron
NM_001303250.3 splice_donor, intron
Scores
1
1
Splicing: ADA: 0.5943
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.39
Genes affected
SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC25A46 | NM_001303250.3 | c.10+2T>G | splice_donor_variant, intron_variant | Intron 1 of 7 | NP_001290179.1 | |||
TMEM232 | XM_006714670.4 | c.-298+473A>C | intron_variant | Intron 1 of 15 | XP_006714733.1 | |||
TMEM232 | XM_011543552.3 | c.-649+473A>C | intron_variant | Intron 1 of 16 | XP_011541854.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000513807.5 | c.-204+2T>G | splice_donor_variant, intron_variant | Intron 1 of 7 | 2 | ENSP00000421134.1 | ||||
TMEM232 | ENST00000515278.6 | c.-298+473A>C | intron_variant | Intron 1 of 6 | 5 | ENSP00000421614.2 | ||||
TMEM232 | ENST00000503527.6 | n.197+473A>C | intron_variant | Intron 1 of 3 | 3 | |||||
SLC25A46 | ENST00000508781.5 | n.112+2T>G | splice_donor_variant, intron_variant | Intron 1 of 7 | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000791 AC: 1AN: 126476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 69308
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GnomAD4 exome AF: 8.82e-7 AC: 1AN: 1134414Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 556450
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GnomAD4 genome Cov.: 32
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32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
Find out detailed SpliceAI scores and Pangolin per-transcript scores at