Variant 11-27093183-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003986.3(BBOX1):c.350G>T(p.Gly117Val) variant causes a missense change. The variant allele was found at a frequency of 0.000264 in 1,612,018 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

BBOX1
NM_003986.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

Variant links:

Genes affected

BBOX1 (HGNC:964): (gamma-butyrobetaine hydroxylase 1) This gene encodes gamma butyrobetaine hydroxylase which catalyzes the formation of L-carnitine from gamma-butyrobetaine, the last step in the L-carnitine biosynthetic pathway. Carnitine is essential for the transport of activated fatty acids across the mitochondrial membrane during mitochondrial beta-oxidation. [provided by RefSeq, Jul 2008]

BBOX1 links:

BBOX1-AS1 (HGNC:50700): (BBOX1 antisense RNA 1)

BBOX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBOX1	NM_003986.3 linkuse as main transcript	c.350G>T	p.Gly117Val	missense_variant	5/9	ENST00000263182.8
BBOX1-AS1	NR_125768.1 linkuse as main transcript	n.378-45871C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBOX1	ENST00000263182.8 linkuse as main transcript	c.350G>T	p.Gly117Val	missense_variant	5/9	5	NM_003986.3	P1
BBOX1-AS1	ENST00000526061.5 linkuse as main transcript	n.345-45871C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000257

AC:

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000501

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

249682

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000364

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000265

AC:

387

AN:

1460040

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000332

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000257

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000501

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000418

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2023

The c.350G>T (p.G117V) alteration is located in exon 5 (coding exon 3) of the BBOX1 gene. This alteration results from a G to T substitution at nucleotide position 350, causing the glycine (G) at amino acid position 117 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.94

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.4

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.5

D;D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.72

MVP

0.97

MPC

0.46

ClinPred

0.81

GERP RS

5.5

Varity_R

0.96

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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