chr19-47228311-C-A

Variant names:

• chr19-47228311-C-A
• NM_014417.5:c.121G>T

Variant summary

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

The NM_014417.5(BBC3):​c.121G>T​(p.Glu41*) variant causes a stop gained 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. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BBC3 NM_014417.5 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	NM_014417.5	MANE Select	c.121G>T	p.Glu41*	stop_gained	Exon 2 of 4	NP_055232.1	Q9BXH1-1
	BBC3	NM_001127240.3		c.224G>T	p.Arg75Leu	missense	Exon 2 of 4	NP_001120712.1	Q96PG8-2
	BBC3	NM_001127241.3		c.89-1557G>T		intron	N/A	NP_001120713.1	Q9BXH1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	ENST00000439096.3	TSL:1 MANE Select	c.121G>T	p.Glu41*	stop_gained	Exon 2 of 4	ENSP00000395862.2	Q9BXH1-1
	BBC3	ENST00000449228.5	TSL:1	c.224G>T	p.Arg75Leu	missense	Exon 2 of 4	ENSP00000404503.1	Q96PG8-2
	BBC3	ENST00000341983.8	TSL:1	c.89-1557G>T		intron	N/A	ENSP00000341155.4	Q9BXH1-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1072694 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 506732

African (AFR) AF: 0.00 AC: 0 AN: 22552

American (AMR) AF: 0.00 AC: 0 AN: 8140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13980

East Asian (EAS) AF: 0.00 AC: 0 AN: 25942

South Asian (SAS) AF: 0.00 AC: 0 AN: 19456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2876

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 915654

Other (OTH) AF: 0.00 AC: 0 AN: 43052

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		1.2
Vest4		0.61
ClinPred		0.49	T
GERP RS		1.8
Varity_R		0.28
Mutation Taster		=138/62	disease causing (fs/PTC)

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

Other links and lift over

hg19: chr19-47731568;