rs14235

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005881.4(BCKDK):c.615G>A(p.Thr205Thr) 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
NM_005881.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.31

Publications

93 publications found

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 Gene-Disease associations (from GenCC):

branched-chain keto acid dehydrogenase kinase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

BCKDK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BCKDK	NM_005881.4 link	c.615G>A	p.Thr205Thr	synonymous_variant	Exon 7 of 12	ENST00000219794.11	NP_005872.2	O14874-1A0A024QZA9
BCKDK	NM_001122957.4 link	c.615G>A	p.Thr205Thr	synonymous_variant	Exon 7 of 11		NP_001116429.1	O14874-3
BCKDK	NM_001271926.3 link	c.615G>A	p.Thr205Thr	synonymous_variant	Exon 7 of 10		NP_001258855.1	O14874-2
BCKDK	XM_017022859.2 link	c.615G>A	p.Thr205Thr	synonymous_variant	Exon 7 of 12		XP_016878348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000219794.11 link	c.615G>A	p.Thr205Thr	synonymous_variant	Exon 7 of 12	1	NM_005881.4	ENSP00000219794.6		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

GnomAD2 exomes

AF:

0.391

AC:

97676

AN:

249502

AF XY:

0.381

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 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

African (AFR)

AF:

0.117

AC:

3933

AN:

33478

American (AMR)

AF:

0.448

AC:

20028

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

12692

AN:

26134

East Asian (EAS)

AF:

0.904

AC:

35869

AN:

39700

South Asian (SAS)

AF:

0.180

AC:

15546

AN:

86252

European-Finnish (FIN)

AF:

0.388

AC:

20635

AN:

53132

Middle Eastern (MID)

AF:

0.489

AC:

2813

AN:

5756

European-Non Finnish (NFE)

AF:

0.364

AC:

404426

AN:

1111948

Other (OTH)

AF:

0.384

AC:

23184

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

21005

42009

63014

84018

105023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12740

25480

38220

50960

63700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.317

AC:

48158

AN:

152030

Hom.:

9633

Cov.:

AF XY:

0.320

AC XY:

23756

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.122

AC:

5053

AN:

41488

American (AMR)

AF:

0.378

AC:

5763

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1718

AN:

3468

East Asian (EAS)

AF:

0.892

AC:

4605

AN:

5164

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4822

European-Finnish (FIN)

AF:

0.390

AC:

4118

AN:

10566

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24714

AN:

67968

Other (OTH)

AF:

0.377

AC:

796

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1511

3022

4534

6045

7556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.372

Hom.:

34526

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

PreventionGenetics, part of Exact Sciences

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. -

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Branched-chain keto acid dehydrogenase kinase deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.9

(source)

DANN

Benign

0.87

PhyloP100

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over