XM_017022859.2:c.1094+1059A>G

Variant names:

• chr16-31113086-A-G
• rs749767
• XM_017022859.2:c.1094+1059A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017022859.2(BCKDK):​c.1094+1059A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,206 control chromosomes in the GnomAD database, including 11,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11355 hom., cov: 33)
• Consequence: BCKDK XM_017022859.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 46 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122957.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCKDK	NM_001122957.4		c.*1055A>G		downstream_gene	N/A	NP_001116429.1
	BCKDK	NM_001271926.3		c.*1055A>G		downstream_gene	N/A	NP_001258855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.368 AC: 56005 AN: 152088 Hom.: 11356 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 56013 AN: 152206 Hom.: 11355 Cov.: 33 AF XY: 0.369 AC XY: 27422 AN XY: 74414

African (AFR) AF: 0.286 AC: 11874 AN: 41534

American (AMR) AF: 0.403 AC: 6161 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4629 AN: 5188

South Asian (SAS) AF: 0.181 AC: 875 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4139 AN: 10586

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25116 AN: 68000

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.377 Hom.: 7595

Bravo AF: 0.379

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.017

Splicing

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

Other links and lift over

dbSNP: rs749767; hg19: chr16-31124407;