3-107716756-G-C

Position:

• chr3-107716756-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142568.3(BBX):​c.312G>C​(p.Arg104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBX NM_001142568.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.500

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37679988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBX	NM_001142568.3	c.312G>C	p.Arg104Ser	missense_variant	5/18	ENST00000325805.13	NP_001136040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13	c.312G>C	p.Arg104Ser	missense_variant	5/18	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

Aug 14, 2024

The c.312G>C (p.R104S) alteration is located in exon 5 (coding exon 2) of the BBX gene. This alteration results from a G to C substitution at nucleotide position 312, causing the arginine (R) at amino acid position 104 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	.;T;T;.;.;T;T;.;.;.;T;.;.
Eigen	Benign	-0.015
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	-0.34	N;.;N;.;N;.;.;.;N;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N;D;N;N;N
REVEL	Uncertain	0.62
Sift	Uncertain	0.019	D;D;D;T;D;T;T;T;D;T;T;T;T
Sift4G	Uncertain	0.047	D;T;D;T;D;T;T;T;D;T;T;T;T
Polyphen		0.052	B;D;D;.;.;.;.;.;B;.;.;.;.
Vest4		0.65
MutPred		0.38		Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);Loss of MoRF binding (P = 0.0106);
MVP		0.96
MPC		0.28
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.29
gMVP		0.52

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: chr3-107435603;