chr8-26383213-C-T

Position:

• chr8-26383213-C-T

Variant summary

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

The NM_004331.3(BNIP3L):​c.83C>T​(p.Pro28Leu) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BNIP3L NM_004331.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

Genes affected

BNIP3L (HGNC:1085): (BCL2 interacting protein 3 like) This gene encodes a protein that belongs to the pro-apoptotic subfamily within the Bcl-2 family of proteins. The encoded protein binds to Bcl-2 and possesses the BH3 domain. The protein directly targets mitochondria and causes apoptotic changes, including loss of membrane potential and the release of cytochrome c. [provided by RefSeq, Feb 2015]

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=0.17926532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP3L	NM_004331.3	c.83C>T	p.Pro28Leu	missense_variant	1/6	ENST00000380629.7	NP_004322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP3L	ENST00000380629.7	c.83C>T	p.Pro28Leu	missense_variant	1/6	1	NM_004331.3	ENSP00000370003	P1
BNIP3L	ENST00000520077.5	c.83C>T	p.Pro28Leu	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000428919
BNIP3L	ENST00000523949.5	c.17C>T	p.Pro6Leu	missense_variant	1/6	3		ENSP00000429171

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Dec 30, 2023

The c.83C>T (p.P28L) alteration is located in exon 1 (coding exon 1) of the BNIP3L gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 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	0.071
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.96	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.15
Sift	Benign	0.092	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.31	B;.
Vest4		0.30
MutPred		0.32		Loss of glycosylation at P28 (P = 0.0236);.;
MVP		0.20
MPC		0.27
ClinPred		0.41	T
GERP RS		4.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.0
Varity_R		0.063
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-26240729; COSMIC: COSV66078005; COSMIC: COSV66078005;