chr16-31109404-G-T

Position:

chr16-31109404-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005881.4(BCKDK):c.181G>T(p.Ala61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,608,256 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

BCKDK
NM_005881.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.32

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045591295).

BP6

Variant 16-31109404-G-T is Benign according to our data. Variant chr16-31109404-G-T is described in ClinVar as [Benign]. Clinvar id is 783737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00269 (409/152292) while in subpopulation AFR AF= 0.00943 (392/41552). AF 95% confidence interval is 0.00866. There are 1 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDK	NM_005881.4 link	c.181G>T	p.Ala61Ser	missense_variant	2/12	ENST00000219794.11	NP_005872.2	O14874-1A0A024QZA9
BCKDK	NM_001122957.4 link	c.181G>T	p.Ala61Ser	missense_variant	2/11		NP_001116429.1	O14874-3
BCKDK	NM_001271926.3 link	c.181G>T	p.Ala61Ser	missense_variant	2/10		NP_001258855.1	O14874-2
BCKDK	XM_017022859.2 link	c.181G>T	p.Ala61Ser	missense_variant	2/12		XP_016878348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000219794.11 link	c.181G>T	p.Ala61Ser	missense_variant	2/12	1	NM_005881.4	ENSP00000219794.6		O14874-1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

410

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000730

AC:

180

AN:

246470

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

133754

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000289

AC:

421

AN:

1455964

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

176

AN XY:

723408

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.00269

AC:

409

AN:

152292

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00943

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00299

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000874

AC:

106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jan 07, 2020

- -

Branched-chain keto acid dehydrogenase kinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 02, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.089

T;.;.;T;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.75

.;T;T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;L;L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.28

N;N;N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.45

T;T;T;T;T;T

Sift4G

Benign

0.81

T;T;T;T;D;T

Polyphen

0.0040

B;.;.;B;.;.

Vest4

0.13

MVP

0.28

MPC

0.51

ClinPred

0.0039

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.75

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