1-100206504-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001918.5(DBT):c.1150A>G(p.Ser384Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,613,388 control chromosomes in the GnomAD database, including 665,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S384S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.88 ( 58729 hom., cov: 31)

Exomes 𝑓: 0.91 ( 607129 hom. )

Consequence

DBT
NM_001918.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.94

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]

DBT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0305434E-6).

BP6

Variant 1-100206504-T-C is Benign according to our data. Variant chr1-100206504-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 128885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-100206504-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBT	NM_001918.5 link	c.1150A>G	p.Ser384Gly	missense_variant	Exon 9 of 11	ENST00000370132.8	NP_001909.4	P11182

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DBT	ENST00000370132.8 link	c.1150A>G	p.Ser384Gly	missense_variant	Exon 9 of 11	1	NM_001918.5	ENSP00000359151.3	P11182
DBT	ENST00000681617.1 link	c.1276A>G	p.Ser426Gly	missense_variant	Exon 10 of 12			ENSP00000505544.1	A0A7P0Z494
DBT	ENST00000681780.1 link	c.607A>G	p.Ser203Gly	missense_variant	Exon 10 of 12			ENSP00000505780.1	A0A7P0T9W1

Frequencies

GnomAD3 genomes

AF:

0.876

AC:

133222

AN:

152050

Hom.:

58703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.917

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.934

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.911

Gnomad OTH

AF:

0.890

GnomAD3 exomes

AF:

0.917

AC:

230704

AN:

251468

Hom.:

106115

AF XY:

0.920

AC XY:

125056

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.763

Gnomad AMR exome

AF:

0.955

Gnomad ASJ exome

AF:

0.917

Gnomad EAS exome

AF:

0.969

Gnomad SAS exome

AF:

0.952

Gnomad FIN exome

AF:

0.931

Gnomad NFE exome

AF:

0.908

Gnomad OTH exome

AF:

0.913

GnomAD4 exome

AF:

0.911

AC:

1331229

AN:

1461220

Hom.:

607129

Cov.:

AF XY:

0.913

AC XY:

663563

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.763

Gnomad4 AMR exome

AF:

0.951

Gnomad4 ASJ exome

AF:

0.915

Gnomad4 EAS exome

AF:

0.980

Gnomad4 SAS exome

AF:

0.952

Gnomad4 FIN exome

AF:

0.929

Gnomad4 NFE exome

AF:

0.907

Gnomad4 OTH exome

AF:

0.909

GnomAD4 genome

AF:

0.876

AC:

133297

AN:

152168

Hom.:

58729

Cov.:

AF XY:

0.880

AC XY:

65449

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.765

Gnomad4 AMR

AF:

0.917

Gnomad4 ASJ

AF:

0.913

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.952

Gnomad4 FIN

AF:

0.934

Gnomad4 NFE

AF:

0.911

Gnomad4 OTH

AF:

0.891

Alfa

AF:

0.907

Hom.:

111723

Bravo

AF:

0.869

TwinsUK

AF:

0.906

AC:

3361

ALSPAC

AF:

0.907

AC:

3495

ESP6500AA

AF:

0.775

AC:

3414

ESP6500EA

AF:

0.902

AC:

7761

ExAC

AF:

0.914

AC:

110942

Asia WGS

AF:

0.926

AC:

3223

AN:

3478

EpiCase

AF:

0.905

EpiControl

AF:

0.904

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Aug 24, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Maple syrup urine disease

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29306928, 14517957, 26232051, 27884173, 9621512, 20981092) -

Maple syrup urine disease type 1A

Benign:1

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.15

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.017

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

3.0

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.042

MPC

0.29

ClinPred

0.00015

GERP RS

4.4

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over