chr5-173144609-G-A

Position:

• chr5-173144609-G-A

Variant summary

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

The NM_001205.3(BNIP1):​c.64G>A​(p.Glu22Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP1 NM_001205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNIP1	NM_001205.3	c.64G>A	p.Glu22Lys	missense_variant	1/6	ENST00000351486.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNIP1	ENST00000351486.10	c.64G>A	p.Glu22Lys	missense_variant	1/6	1	NM_001205.3	P1
	ENST00000521251.1	n.81-32C>T		intron_variant, non_coding_transcript_variant		5

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

Oct 28, 2023

The c.64G>A (p.E22K) alteration is located in exon 1 (coding exon 1) of the BNIP1 gene. This alteration results from a G to A substitution at nucleotide position 64, causing the glutamic acid (E) at amino acid position 22 to be replaced by a lysine (K). 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	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	.;T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.7	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.016	D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		0.99	D;P;P;D
Vest4		0.72
MutPred		0.36		Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);
MVP		0.77
MPC		0.47
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.64
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr5-172571612;