chr5-173154384-A-C

Position:

• chr5-173154384-A-C

Variant summary

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

The NM_001205.3(BNIP1):​c.240A>C​(p.Glu80Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP1 NM_001205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.342

Genes affected

BNIP1 (HGNC:1082): (BCL2 interacting protein 1) This gene is a member of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. It interacts with the E1B 19 kDa protein, which protects cells from virally-induced cell death. The encoded protein also interacts with E1B 19 kDa-like sequences of BCL2, another apoptotic protector. In addition, this protein is involved in vesicle transport into the endoplasmic reticulum. Alternative splicing of this gene results in four protein products with identical N- and C-termini. [provided by RefSeq, Mar 2011]

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=0.13868493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP1	NM_001205.3	c.240A>C	p.Glu80Asp	missense_variant	3/6	ENST00000351486.10	NP_001196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP1	ENST00000351486.10	c.240A>C	p.Glu80Asp	missense_variant	3/6	1	NM_001205.3	ENSP00000239215.7
BNIP1	ENST00000231668.13	c.369A>C	p.Glu123Asp	missense_variant	4/7	1		ENSP00000231668.9
BNIP1	ENST00000352523.10	c.369A>C	p.Glu123Asp	missense_variant	4/6	1		ENSP00000239214.8
BNIP1	ENST00000393770.4	c.240A>C	p.Glu80Asp	missense_variant	3/5	1		ENSP00000377365.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 04, 2024

The c.369A>C (p.E123D) alteration is located in exon 4 (coding exon 4) of the BNIP1 gene. This alteration results from a A to C substitution at nucleotide position 369, causing the glutamic acid (E) at amino acid position 123 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	.;T;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;T;D;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.61	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.0050	B;B;B;B
Vest4		0.58
MutPred		0.29		.;Loss of methylation at K85 (P = 0.1542);.;Loss of methylation at K85 (P = 0.1542);
MVP		0.36
MPC		0.32
ClinPred		0.40	T
GERP RS		0.49
Varity_R		0.10
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: chr5-172581387;