3-107744682-A-C

Position:

• chr3-107744682-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142568.3(BBX):​c.722A>C​(p.Gln241Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBX NM_001142568.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBX	NM_001142568.3	c.722A>C	p.Gln241Pro	missense_variant	8/18	ENST00000325805.13	NP_001136040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13	c.722A>C	p.Gln241Pro	missense_variant	8/18	1	NM_001142568.3	ENSP00000319974.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.722A>C (p.Q241P) alteration is located in exon 8 (coding exon 5) of the BBX gene. This alteration results from a A to C substitution at nucleotide position 722, causing the glutamine (Q) at amino acid position 241 to be replaced by a proline (P). 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	0.087
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	.;T;T;.;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	.;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.50	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.81	L;.;L;L;.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Uncertain	0.64
Sift	Uncertain	0.011	D;D;D;D;D;D
Sift4G	Benign	0.26	T;T;T;D;T;T
Polyphen		0.95	P;D;B;.;.;P
Vest4		0.57
MutPred		0.24		Gain of glycosylation at S243 (P = 0.0072);Gain of glycosylation at S243 (P = 0.0072);Gain of glycosylation at S243 (P = 0.0072);Gain of glycosylation at S243 (P = 0.0072);Gain of glycosylation at S243 (P = 0.0072);Gain of glycosylation at S243 (P = 0.0072);
MVP		0.83
MPC		0.50
ClinPred		0.73	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-107463529;