chr3-107728787-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001142568.3(BBX):​c.428C>A​(p.Ala143Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A143G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

10
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.36

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBXNM_001142568.3 linkc.428C>A p.Ala143Glu missense_variant Exon 6 of 18 ENST00000325805.13 NP_001136040.1 Q8WY36-1A8K6U2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BBXENST00000325805.13 linkc.428C>A p.Ala143Glu missense_variant Exon 6 of 18 1 NM_001142568.3 ENSP00000319974.8 Q8WY36-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460774
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726624
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33408
American (AMR)
AF:
0.00
AC:
0
AN:
44574
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26072
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39676
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86070
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111478
Other (OTH)
AF:
0.00
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.68
.;D;D;.;.;D;D;.;.;.;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
0.34
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Benign
0.77
N;.;N;.;N;.;.;.;N;.;.;.
PhyloP100
7.4
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-4.5
D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.81
Sift
Benign
0.061
T;T;D;T;T;D;T;T;T;T;T;T
Sift4G
Uncertain
0.025
D;D;D;T;T;D;T;T;D;T;T;T
Polyphen
0.47
P;D;D;.;.;.;.;.;P;.;.;.
Vest4
0.86
MutPred
0.49
Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);Gain of ubiquitination at K148 (P = 0.0301);
MVP
0.93
MPC
0.70
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.73
gMVP
0.69
Mutation Taster
=28/72
disease causing

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

Other links and lift over

dbSNP: rs1255377082; hg19: chr3-107447634; API