Variant 6-80106696-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate

The NM_183050.4(BCKDHB):c.3G>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000712 in 1,403,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

BCKDHB
NM_183050.4 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.46

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]

BCKDHB links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 14 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PS1

Another start lost variant in NM_183050.4 (BCKDHB) was described as [Likely_pathogenic] in ClinVar as 551456

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 6-80106696-G-A is Pathogenic according to our data. Variant chr6-80106696-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 224057.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCKDHB	NM_183050.4 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/10	ENST00000320393.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCKDHB	ENST00000320393.9 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/10	1	NM_183050.4	P1	P21953-1
BCKDHB	ENST00000356489.9 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/11	1		P1	P21953-1
BCKDHB	ENST00000369760.8 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/6	3			P21953-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1403514

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Maple syrup urine disease

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital

Jan 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

.;T;T

Eigen

Benign

0.0083

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.90

D;.;D

M_CAP

Pathogenic

1.0

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Uncertain

0.46

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-0.48

N;N;N

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.12

.;B;B

Vest4

0.91

MutPred

0.87

Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);Loss of solvent accessibility (P = 0.0155);

MVP

0.98

ClinPred

1.0

GERP RS

5.3

Varity_R

0.96

gMVP

0.61

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