Variant rs14235 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000219794.11(BCKDK):c.615G>A(p.Thr205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,534 control chromosomes in the GnomAD database, including 118,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9633 hom., cov: 32)

Exomes 𝑓: 0.37 ( 109015 hom. )

Consequence

BCKDK
ENST00000219794.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.31

Variant links:

Genes affected

BCKDK (HGNC:16902): (branched chain keto acid dehydrogenase kinase) The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

BCKDK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 16-31110472-G-A is Benign according to our data. Variant chr16-31110472-G-A is described in ClinVar as [Benign]. Clinvar id is 128521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BCKDK	NM_005881.4 linkuse as main transcript	c.615G>A	p.Thr205=	synonymous_variant	7/12	ENST00000219794.11	NP_005872.2
BCKDK	NM_001122957.4 linkuse as main transcript	c.615G>A	p.Thr205=	synonymous_variant	7/11		NP_001116429.1
BCKDK	NM_001271926.3 linkuse as main transcript	c.615G>A	p.Thr205=	synonymous_variant	7/10		NP_001258855.1
BCKDK	XM_017022859.2 linkuse as main transcript	c.615G>A	p.Thr205=	synonymous_variant	7/12		XP_016878348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000219794.11 linkuse as main transcript	c.615G>A	p.Thr205=	synonymous_variant	7/12	1	NM_005881.4	ENSP00000219794	P1	O14874-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48154

AN:

151912

Hom.:

9632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.378

GnomAD3 exomes

AF:

0.391

AC:

97676

AN:

249502

Hom.:

23036

AF XY:

0.381

AC XY:

51458

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.485

Gnomad EAS exome

AF:

0.895

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.369

AC:

539126

AN:

1461504

Hom.:

109015

Cov.:

AF XY:

0.365

AC XY:

265029

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.486

Gnomad4 EAS exome

AF:

0.904

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.384

GnomAD4 genome

AF:

0.317

AC:

48158

AN:

152030

Hom.:

9633

Cov.:

AF XY:

0.320

AC XY:

23756

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.892

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.373

Hom.:

15797

Bravo

AF:

0.321

Asia WGS

AF:

0.459

AC:

1599

AN:

3478

EpiCase

AF:

0.382

EpiControl

AF:

0.390

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Branched-chain keto acid dehydrogenase kinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.9

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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