chr3-107710485-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142568.3(BBX):​c.25G>T​(p.Asp9Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D9N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.20

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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBXNM_001142568.3 linkc.25G>T p.Asp9Tyr 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
BBXENST00000325805.13 linkc.25G>T p.Asp9Tyr missense_variant Exon 4 of 18 1 NM_001142568.3 ENSP00000319974.8 Q8WY36-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151896
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461332
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726966
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33458
American (AMR)
AF:
0.00
AC:
0
AN:
44696
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39660
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86190
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111648
Other (OTH)
AF:
0.00
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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
AF:
0.00000658
AC:
1
AN:
151896
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74148
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41350
American (AMR)
AF:
0.00
AC:
0
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10556
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67984
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
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

Genome 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
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.091
.;T;T;.;.;.;T;T;.;T;T;.;.;.;T;.;.;T;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.29
D
MetaRNN
Uncertain
0.60
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Benign
0.90
L;.;L;.;L;.;.;.;.;.;.;.;L;.;.;.;.;.;.
PhyloP100
9.2
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-4.5
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;.;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.
Vest4
0.53
MutPred
0.15
Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);Gain of glycosylation at S11 (P = 0.0087);
MVP
0.71
MPC
0.66
ClinPred
0.98
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.79
gMVP
0.23
Mutation Taster
=44/56
disease causing

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

Other links and lift over

dbSNP: rs528150696; hg19: chr3-107429332; API