Genetic Variant BBC3:p.Thr52Ile (chr19-47228277-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014417.5(BBC3):c.155C>T(p.Thr52Ile) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BBC3
NM_014417.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23

Publications

0 publications found

Variant links:

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]

BBC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117981434).

BP6

Variant 19-47228277-G-A is Benign according to our data. Variant chr19-47228277-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3479894.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBC3	NM_014417.5	MANE Select	c.155C>T	p.Thr52Ile	missense	Exon 2 of 4	NP_055232.1	Q9BXH1-1
BBC3	NM_001127240.3		c.258C>T	p.His86His	synonymous	Exon 2 of 4	NP_001120712.1	Q96PG8-2
BBC3	NM_001127241.3		c.89-1523C>T		intron	N/A	NP_001120713.1	Q9BXH1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBC3	ENST00000439096.3	TSL:1 MANE Select	c.155C>T	p.Thr52Ile	missense	Exon 2 of 4	ENSP00000395862.2	Q9BXH1-1
BBC3	ENST00000449228.5	TSL:1	c.258C>T	p.His86His	synonymous	Exon 2 of 4	ENSP00000404503.1	Q96PG8-2
BBC3	ENST00000341983.8	TSL:1	c.89-1523C>T		intron	N/A	ENSP00000341155.4	Q9BXH1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1065552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

503360

African (AFR)

AF:

0.00

AC:

AN:

22330

American (AMR)

AF:

0.00

AC:

AN:

7914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13602

East Asian (EAS)

AF:

0.00

AC:

AN:

25268

South Asian (SAS)

AF:

0.00

AC:

AN:

19384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2844

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

910784

Other (OTH)

AF:

0.00

AC:

AN:

42486

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.31

M_CAP

Benign

0.041

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

1.2

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

REVEL

Benign

0.033

Sift

Uncertain

0.027

Sift4G

Uncertain

0.034

Polyphen

0.048

Vest4

0.15

MutPred

0.24

Loss of glycosylation at T52 (P = 0.0018)

MVP

0.59

ClinPred

0.48

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over