Variant 3-107710480-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142568.3(BBX):c.20A>G(p.Asn7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000057 in 1,613,502 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

BBX
NM_001142568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

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:

BBX (HGNC:):

BBX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14019951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBX	NM_001142568.3 linkuse as main transcript	c.20A>G	p.Asn7Ser	missense_variant	4/18	ENST00000325805.13	NP_001136040.1	Q8WY36-1A8K6U2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13 linkuse as main transcript	c.20A>G	p.Asn7Ser	missense_variant	4/18	1	NM_001142568.3	ENSP00000319974.8		Q8WY36-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000877

AC:

AN:

250834

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1461342

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

726976

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:

0.000638

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Aug 02, 2023

The c.20A>G (p.N7S) alteration is located in exon 4 (coding exon 1) of the BBX gene. This alteration results from a A to G substitution at nucleotide position 20, causing the asparagine (N) at amino acid position 7 to be replaced by a serine (S). 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

0.085

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

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

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.077

MetaRNN

Benign

0.14

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

MetaSVM

Pathogenic

1.2

MutationAssessor

Benign

0.97

L;.;L;.;L;.;.;.;.;.;.;.;L;.;.;.;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

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

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.053

T;T;T;T;D;.;T;T;T;T;T;D;T;T;T;D;T;T;T

Polyphen

0.99

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

Vest4

0.28

MutPred

0.12

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

0.89

MPC

0.12

ClinPred

0.28

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.074

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