Variant chr5-173154400-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001205.3(BNIP1):c.256A>C(p.Lys86Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

BNIP1
NM_001205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Variant links:

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]

BNIP1 links:

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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=0.12903744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNIP1	NM_001205.3 linkuse as main transcript	c.256A>C	p.Lys86Gln	missense_variant	3/6	ENST00000351486.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNIP1	ENST00000351486.10 linkuse as main transcript	c.256A>C	p.Lys86Gln	missense_variant	3/6	1	NM_001205.3	P1	Q12981-4
BNIP1	ENST00000231668.13 linkuse as main transcript	c.385A>C	p.Lys129Gln	missense_variant	4/7	1			Q12981-1
BNIP1	ENST00000352523.10 linkuse as main transcript	c.385A>C	p.Lys129Gln	missense_variant	4/6	1			Q12981-3
BNIP1	ENST00000393770.4 linkuse as main transcript	c.256A>C	p.Lys86Gln	missense_variant	3/5	1			Q12981-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000999

AC:

AN:

250134

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461200

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000560

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.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.385A>C (p.K129Q) 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 385, causing the lysine (K) at amino acid position 129 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

.;T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.93

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.86

P;P;P;D

Vest4

0.50

MutPred

0.46

.;Loss of ubiquitination at K86 (P = 0.003);.;Loss of ubiquitination at K86 (P = 0.003);

MVP

0.60

MPC

0.78

ClinPred

0.37

GERP RS

5.5

Varity_R

0.21

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over