19-47228354-C-G

Variant names:

• chr19-47228354-C-G
• rs767230320
• ENST00000449228.5:c.181G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127240.3(BBC3):​c.181G>C​(p.Ala61Pro) 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. 13/19 in silico tools predict 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: BBC3 NM_001127240.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

Genes affected

BBC3 (HGNC:17868): (BCL2 binding component 3) This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

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=0.11361641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	NM_014417.5	c.78G>C	p.Pro26Pro	synonymous_variant	Exon 2 of 4	ENST00000439096.3	NP_055232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBC3	ENST00000449228.5	c.181G>C	p.Ala61Pro	missense_variant	Exon 2 of 4	1		ENSP00000404503.1
BBC3	ENST00000439096.3	c.78G>C	p.Pro26Pro	synonymous_variant	Exon 2 of 4	1	NM_014417.5	ENSP00000395862.2
BBC3	ENST00000341983.8	c.89-1600G>C		intron_variant	Intron 1 of 2	1		ENSP00000341155.4
BBC3	ENST00000300880.11	c.88+4161G>C		intron_variant	Intron 1 of 1	1		ENSP00000300880.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.036
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.29	T
Vest4		0.15
MutPred		0.23		Gain of glycosylation at A61 (P = 0.0051);
MVP		0.27
MPC		1.6
ClinPred		0.087	T
GERP RS		-5.8
Varity_R		0.30
gMVP		0.075

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

LitVar

Other links and lift over

dbSNP: rs767230320; hg19: chr19-47731611;