10-131981784-C-A

Variant names:

• chr10-131981784-C-A
• rs1345848637
• NM_004052.4:c.23G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0720

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]

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=0.107913285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNIP3	NM_004052.4	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 6	ENST00000368636.9	NP_004043.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNIP3	ENST00000368636.9	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 6	1	NM_004052.4	ENSP00000357625.6
BNIP3	ENST00000540159.4	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 5	1		ENSP00000446145.3
BNIP3	ENST00000633835.2	c.23G>T	p.Gly8Val	missense_variant	Exon 1 of 6	3		ENSP00000487769.2
BNIP3	ENST00000631806.1	n.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

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

Other links and lift over

dbSNP: rs1345848637; hg19: chr10-133795288;