16-31106092-C-T

Variant names:

• chr16-31106092-C-T
• rs2032915
• ENST00000394951.5:c.-638C>T

Variant summary

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

The ENST00000394951.5(BCKDK):​c.-638C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,168 control chromosomes in the GnomAD database, including 9,414 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 0.30 (9413 hom., cov: 32)
  • Exomes 𝑓: 0.37 (1 hom.)
• Consequence: BCKDK ENST00000394951.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 35 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCKDK	ENST00000394951.5	c.-638C>T		upstream_gene_variant		5		ENSP00000378405.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45970 AN: 152022 Hom.: 9412 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.367 AC: 11 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.346 AC: 9 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.302 AC: 45970 AN: 152138 Hom.: 9413 Cov.: 32 AF XY: 0.305 AC XY: 22716 AN XY: 74358

African (AFR) AF: 0.0713 AC: 2961 AN: 41518

American (AMR) AF: 0.371 AC: 5670 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1722 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4611 AN: 5168

South Asian (SAS) AF: 0.176 AC: 849 AN: 4828

European-Finnish (FIN) AF: 0.390 AC: 4117 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24712 AN: 67980

Other (OTH) AF: 0.368 AC: 778 AN: 2114

Alfa AF: 0.363 Hom.: 4237

Bravo AF: 0.304

Asia WGS AF: 0.455 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.38
PromoterAI		0.064	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2032915; hg19: chr16-31117413;