NM_138723.2:c.167G>T

Variant names:

• chr12-12079472-G-T
• NM_138723.2:c.167G>T

Variant summary

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

The NM_138723.2(BCL2L14):​c.167G>T​(p.Arg56Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BCL2L14 NM_138723.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

Genes affected

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

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=0.068802804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L14	NM_138723.2	c.167G>T	p.Arg56Met	missense_variant	Exon 2 of 6	ENST00000308721.9	NP_620049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L14	ENST00000308721.9	c.167G>T	p.Arg56Met	missense_variant	Exon 2 of 6	1	NM_138723.2	ENSP00000309132.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.4
DANN	Benign	0.94
DEOGEN2	Benign	0.081	T;T;T;T;T;T;.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.069	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.;L;L;L;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.5	.;.;.;D;N;N;D;.
REVEL	Benign	0.059
Sift	Uncertain	0.0040	.;.;.;D;D;D;D;.
Sift4G	Uncertain	0.0060	D;D;D;.;D;D;D;D
Polyphen		0.50	P;.;.;.;P;P;P;.
Vest4		0.15
MutPred		0.32		Gain of catalytic residue at L58 (P = 0.0051);.;Gain of catalytic residue at L58 (P = 0.0051);.;Gain of catalytic residue at L58 (P = 0.0051);Gain of catalytic residue at L58 (P = 0.0051);Gain of catalytic residue at L58 (P = 0.0051);Gain of catalytic residue at L58 (P = 0.0051);
MVP		0.23
MPC		0.28
ClinPred		0.41	T
GERP RS		-1.1
Varity_R		0.073
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-12232406;