3-107710602-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001142568.3(BBX):c.142G>A(p.Glu48Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,434 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20

Publications

1 publications found

Variant links:

Genes affected

BBX (HGNC:14422): (BBX high mobility group box domain containing) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BBX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29064894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBX	NM_001142568.3 link	c.142G>A	p.Glu48Lys	missense_variant	Exon 4 of 18	ENST00000325805.13	NP_001136040.1	Q8WY36-1A8K6U2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13 link	c.142G>A	p.Glu48Lys	missense_variant	Exon 4 of 18	1	NM_001142568.3	ENSP00000319974.8		Q8WY36-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000564

AC:

AN:

248404

AF XY:

0.0000521

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000804

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1460328

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726378

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39562

South Asian (SAS)

AF:

0.0000233

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1111166

Other (OTH)

AF:

0.0000332

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.142G>A (p.E48K) alteration is located in exon 4 (coding exon 1) of the BBX gene. This alteration results from a G to A substitution at nucleotide position 142, causing the glutamic acid (E) at amino acid position 48 to be replaced by a lysine (K). 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

Benign

0.28

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

.;T;T;.;.;T;T;.;T;T;.;.;.;T;.;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

0.69

N;.;N;.;N;.;.;.;.;.;.;N;.;.;.;.;.

PhyloP100

9.2

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

N;N;N;N;N;D;N;D;N;N;N;N;N;N;N;D;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.0070

D;D;D;T;D;D;T;D;D;T;D;D;T;T;T;D;T

Sift4G

Benign

0.22

T;T;T;T;T;T;T;D;T;T;T;T;T;T;T;T;T

Polyphen

0.11

B;B;B;.;.;.;.;.;.;.;.;B;.;.;.;.;.

Vest4

0.60

MutPred

0.19

Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);Gain of ubiquitination at E48 (P = 0.0048);

MVP

0.57

MPC

0.23

ClinPred

0.19

GERP RS

5.7

Varity_R

0.22

gMVP

0.26

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-107710602-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over