Variant 22-17689076-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015367.4(BCL2L13):c.320T>G(p.Leu107Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000828 in 1,614,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 1 hom. )

Consequence

BCL2L13
NM_015367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Variant links:

Genes affected

BCL2L13 (HGNC:17164): (BCL2 like 13) This gene encodes a mitochondrially-localized protein with conserved B-cell lymphoma 2 homology motifs. Overexpression of the encoded protein results in apoptosis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

BCL2L13 links:

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ACMG classification

Classification made for transcript

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=0.12053445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L13	NM_015367.4 linkuse as main transcript	c.320T>G	p.Leu107Arg	missense_variant	4/7	ENST00000317582.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L13	ENST00000317582.10 linkuse as main transcript	c.320T>G	p.Leu107Arg	missense_variant	4/7	1	NM_015367.4	A2	Q9BXK5-1

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000497

AC:

125

AN:

251418

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000818

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000858

AC:

1254

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000853

AC XY:

620

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000545

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000799

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000949

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.320T>G (p.L107R) alteration is located in exon 4 (coding exon 3) of the BCL2L13 gene. This alteration results from a T to G substitution at nucleotide position 320, causing the leucine (L) at amino acid position 107 to be replaced by an arginine (R). 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

0.31

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.040

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.;.;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.1

D;.;.;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;.;.;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;D

Vest4

0.76

MVP

0.46

MPC

0.68

ClinPred

0.12

GERP RS

5.7

Varity_R

0.78

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over