Menu
GeneBe

16-31109289-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_005881.4(BCKDK):c.66A>T(p.Gly22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,601,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

BCKDK
NM_005881.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-31109289-A-T is Benign according to our data. Variant chr16-31109289-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1620858.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.144 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000033 (5/151610) while in subpopulation SAS AF= 0.000838 (4/4776). AF 95% confidence interval is 0.000286. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCKDKNM_005881.4 linkuse as main transcriptc.66A>T p.Gly22= synonymous_variant 2/12 ENST00000219794.11
BCKDKNM_001122957.4 linkuse as main transcriptc.66A>T p.Gly22= synonymous_variant 2/11
BCKDKNM_001271926.3 linkuse as main transcriptc.66A>T p.Gly22= synonymous_variant 2/10
BCKDKXM_017022859.2 linkuse as main transcriptc.66A>T p.Gly22= synonymous_variant 2/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCKDKENST00000219794.11 linkuse as main transcriptc.66A>T p.Gly22= synonymous_variant 2/121 NM_005881.4 P1O14874-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000396
AC:
6
AN:
151492
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000837
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000961
GnomAD3 exomes
AF:
0.000112
AC:
26
AN:
231174
Hom.:
0
AF XY:
0.000134
AC XY:
17
AN XY:
127338
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000120
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000472
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000389
Gnomad OTH exome
AF:
0.000705
GnomAD4 exome
AF:
0.0000386
AC:
56
AN:
1449784
Hom.:
0
Cov.:
33
AF XY:
0.0000555
AC XY:
40
AN XY:
720176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000160
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000421
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000542
Gnomad4 OTH exome
AF:
0.0000669
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000330
AC:
5
AN:
151610
Hom.:
0
Cov.:
32
AF XY:
0.0000540
AC XY:
4
AN XY:
74106
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000838
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Branched-chain keto acid dehydrogenase kinase deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeAug 24, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
5.1
Dann
Benign
0.62
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs775340971; hg19: chr16-31120610; API