NM_138723.2:c.332A>G

Variant names:

• chr12-12079637-A-G
• rs772117186
• NM_138723.2:c.332A>G

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.332A>G​(p.Lys111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: BCL2L14 NM_138723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.922
• Publications: 1 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=0.10421169).

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.332A>G	p.Lys111Arg	missense	Exon 2 of 6	NP_620049.1	Q9BZR8-1
	BCL2L14	NM_001370268.1		c.332A>G	p.Lys111Arg	missense	Exon 3 of 7	NP_001357197.1	Q9BZR8-1
	BCL2L14	NM_001370269.1		c.332A>G	p.Lys111Arg	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.332A>G	p.Lys111Arg	missense	Exon 2 of 6	ENSP00000309132.4	Q9BZR8-1
	BCL2L14	ENST00000396367.5	TSL:1	c.332A>G	p.Lys111Arg	missense	Exon 2 of 6	ENSP00000379653.1	Q9BZR8-1
	BCL2L14	ENST00000266434.8	TSL:1	c.332A>G	p.Lys111Arg	missense	Exon 2 of 6	ENSP00000266434.4	Q9BZR8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251210 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727226

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: 53394

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

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1112006

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.97
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.92
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.36	T
Polyphen		0.59	P
Vest4		0.032
MutPred		0.18		Loss of ubiquitination at K111 (P = 0.0017)
MVP		0.49
MPC		0.11
ClinPred		0.074	T
GERP RS		-3.3
PromoterAI		-0.065	Neutral
Varity_R		0.031
gMVP		0.042
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs772117186; hg19: chr12-12232571;