12-12079472-G-T

Variant names:

• chr12-12079472-G-T
• rs371514083
• NM_138723.2:c.167G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56K) has been classified as Likely benign.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068802804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138723.2. 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
	BCL2L14	NM_138723.2	MANE Select	c.167G>T	p.Arg56Met	missense	Exon 2 of 6	NP_620049.1	Q9BZR8-1
	BCL2L14	NM_001370268.1		c.167G>T	p.Arg56Met	missense	Exon 3 of 7	NP_001357197.1	Q9BZR8-1
	BCL2L14	NM_001370269.1		c.167G>T	p.Arg56Met	missense	Exon 4 of 8	NP_001357198.1	Q9BZR8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L14	ENST00000308721.9	TSL:1 MANE Select	c.167G>T	p.Arg56Met	missense	Exon 2 of 6	ENSP00000309132.4	Q9BZR8-1
	BCL2L14	ENST00000396367.5	TSL:1	c.167G>T	p.Arg56Met	missense	Exon 2 of 6	ENSP00000379653.1	Q9BZR8-1
	BCL2L14	ENST00000266434.8	TSL:1	c.167G>T	p.Arg56Met	missense	Exon 2 of 6	ENSP00000266434.4	Q9BZR8-2

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.78
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.059
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.50	P
Vest4		0.15
MutPred		0.32		Gain of catalytic residue at L58 (P = 0.0051)
MVP		0.23
MPC		0.28
ClinPred		0.41	T
GERP RS		-1.1
PromoterAI		0.074	Neutral
Varity_R		0.073
gMVP		0.18
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs371514083; hg19: chr12-12232406;