10-131981784-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004052.4(BNIP3):​c.23G>T​(p.Gly8Val) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G8R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BNIP3
NM_004052.4 missense

Scores

4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0720
Variant links:
Genes affected
BNIP3 (HGNC:1084): (BCL2 interacting protein 3) This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.107913285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BNIP3NM_004052.4 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 6 ENST00000368636.9 NP_004043.4 Q12983Q6NVY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BNIP3ENST00000368636.9 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 6 1 NM_004052.4 ENSP00000357625.6 Q12983
BNIP3ENST00000540159.4 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 5 1 ENSP00000446145.3 B4DHJ7
BNIP3ENST00000633835.2 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 6 3 ENSP00000487769.2 A0A0J9YW18
BNIP3ENST00000631806.1 linkn.182G>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1331062
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
656660
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.23G>T (p.G8V) alteration is located in exon 1 (coding exon 1) of the BNIP3 gene. This alteration results from a G to T substitution at nucleotide position 23, causing the glycine (G) at amino acid position 8 to be replaced by a valine (V). 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
0.085
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
15
DANN
Uncertain
0.98
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.60
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.92
T
PrimateAI
Uncertain
0.71
T
REVEL
Benign
0.076
Sift4G
Uncertain
0.046
D;T
Vest4
0.12
MVP
0.21
MPC
0.68
ClinPred
0.24
T
GERP RS
1.3
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1
Varity_R
0.064
gMVP
0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1345848637; hg19: chr10-133795288; API