chr8-26383204-C-G

Position:

• chr8-26383204-C-G

Variant summary

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

The NM_004331.3(BNIP3L):​c.74C>G​(p.Ser25Cys) 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. 14/20 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: 2.46

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=0.07261518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP3L	NM_004331.3	c.74C>G	p.Ser25Cys	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.74C>G	p.Ser25Cys	missense_variant	1/6	1	NM_004331.3	ENSP00000370003.2
BNIP3L	ENST00000520077.5	n.74C>G		non_coding_transcript_exon_variant	1/4	1		ENSP00000428919.1
BNIP3L	ENST00000523949.5	c.8C>G	p.Ser3Cys	missense_variant	1/6	3		ENSP00000429171.1

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

Jan 30, 2024

The c.74C>G (p.S25C) alteration is located in exon 1 (coding exon 1) of the BNIP3L gene. This alteration results from a C to G substitution at nucleotide position 74, causing the serine (S) at amino acid position 25 to be replaced by a cysteine (C). 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	0.078
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.037
Sift	Benign	0.056	T;D
Sift4G	Benign	0.074	T;D
Polyphen		0.031	B;.
Vest4		0.17
MutPred		0.33		Loss of glycosylation at S25 (P = 0.0113);.;
MVP		0.067
MPC		0.26
ClinPred		0.26	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.26

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: chr8-26240720;