chr6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_183050.4(BCKDHB):​c.-22_4del variant causes a start lost, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BCKDHB
NM_183050.4 start_lost, 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.885
Variant links:
Genes affected
BCKDHB (HGNC:987): (branched chain keto acid dehydrogenase E1 subunit beta) This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T is Pathogenic according to our data. Variant chr6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 558247.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCKDHBNM_183050.4 linkuse as main transcriptc.-22_4del start_lost, 5_prime_UTR_variant 1/10 ENST00000320393.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCKDHBENST00000320393.9 linkuse as main transcriptc.-22_4del start_lost, 5_prime_UTR_variant 1/101 NM_183050.4 P1P21953-1
BCKDHBENST00000356489.9 linkuse as main transcriptc.-22_4del start_lost, 5_prime_UTR_variant 1/111 P1P21953-1
BCKDHBENST00000369760.8 linkuse as main transcriptc.-22_4del start_lost, 5_prime_UTR_variant 1/63 P21953-2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Maple syrup urine disease Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCounsylMay 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs1582146275; hg19: chr6-80816387; API