rs121965000

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

Scores

2
1
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.01
Variant links:
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]

Genome browser will be placed here

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
DBTNM_001918.5 linkuse as main transcriptc.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
DBTENST00000370132.8 linkuse as main transcriptc.1448G>T p.Ter483LeuextTer7 stop_lost 11/111 NM_001918.5 ENSP00000359151 P1
DBTENST00000681617.1 linkuse as main transcriptc.1574G>T p.Ter525LeuextTer7 stop_lost 12/12 ENSP00000505544
DBTENST00000681780.1 linkuse as main transcriptc.905G>T p.Ter302LeuextTer7 stop_lost 12/12 ENSP00000505780

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151922
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151922
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74206
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 providedliterature onlyOMIMJan 01, 1998- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Benign
0.75
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.96
D
MutationTaster
Benign
9.5e-9
A
Vest4
0.081
GERP RS
4.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121965000; hg19: chr1-100661812; API