chr19-49667024-C-T

Position:

• chr19-49667024-C-T

Variant summary

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

The NM_138639.2(BCL2L12):​c.113C>T​(p.Pro38Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCL2L12 NM_138639.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.930

Genes affected

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

BCL2L12 (HGNC:):

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=0.08736074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L12	NM_138639.2	c.113C>T	p.Pro38Leu	missense_variant	3/7	ENST00000246784.8	NP_619580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L12	ENST00000246784.8	c.113C>T	p.Pro38Leu	missense_variant	3/7	1	NM_138639.2	ENSP00000246784.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 28, 2024

The c.365C>T (p.P122L) alteration is located in exon 3 (coding exon 3) of the BCL2L12 gene. This alteration results from a C to T substitution at nucleotide position 365, causing the proline (P) at amino acid position 122 to be replaced by a leucine (L). 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	0.086
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.77
DEOGEN2	Benign	0.19	T;T;T;.;T;T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.031	N
LIST_S2	Uncertain	0.86	D;D;D;T;.;D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.087	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;.;.;L;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	.;.;.;D;D;.;.;.
REVEL	Benign	0.039
Sift	Benign	0.053	.;.;.;T;T;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		0.0080	B;.;.;.;B;.;.;.
Vest4		0.23
MutPred		0.081		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);.;Loss of relative solvent accessibility (P = 0.0186);.;.;.;
MVP		0.28
MPC		0.21
ClinPred		0.073	T
GERP RS		2.6
Varity_R		0.064
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-50170281;