rs121965000
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_001918.5(DBT):c.1448G>T(p.Ter483LeuextTer7) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
DBT
NM_001918.5 stop_lost
NM_001918.5 stop_lost
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 2.01
Genes affected
DBT (HGNC:2698): (dihydrolipoamide branched chain transacylase E2) The branched-chain alpha-keto acid dehydrogenase complex (BCKD) is an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. This gene encodes the transacylase (E2) subunit. Mutations in this gene result in maple syrup urine disease, type 2. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_001918.5 Downstream stopcodon found after 55 codons.
PP5
Variant 1-100196256-C-A is Pathogenic according to our data. Variant chr1-100196256-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11947.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DBT | NM_001918.5 | c.1448G>T | p.Ter483LeuextTer7 | stop_lost | 11/11 | ENST00000370132.8 | NP_001909.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DBT | ENST00000370132.8 | c.1448G>T | p.Ter483LeuextTer7 | stop_lost | 11/11 | 1 | NM_001918.5 | ENSP00000359151 | P1 | |
DBT | ENST00000681617.1 | c.1574G>T | p.Ter525LeuextTer7 | stop_lost | 12/12 | ENSP00000505544 | ||||
DBT | ENST00000681780.1 | c.905G>T | p.Ter302LeuextTer7 | stop_lost | 12/12 | ENSP00000505780 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151922Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 31
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151922Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74206
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Maple syrup urine disease type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1998 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
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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