Genetic Variant BNIP3:p.Thr84Asn (chr10-131973065-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004052.4(BNIP3):c.251C>A(p.Thr84Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T84I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BNIP3
NM_004052.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.726

Publications

0 publications found

Variant links:

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]

BNIP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036356002).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004052.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP3	NM_004052.4	MANE Select	c.251C>A	p.Thr84Asn	missense	Exon 3 of 6	NP_004043.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BNIP3	ENST00000368636.9	TSL:1 MANE Select	c.251C>A	p.Thr84Asn	missense	Exon 3 of 6	ENSP00000357625.6	Q12983
BNIP3	ENST00000540159.4	TSL:1	c.251C>A	p.Thr84Asn	missense	Exon 3 of 5	ENSP00000446145.3	B4DHJ7
BNIP3	ENST00000924284.1		c.251C>A	p.Thr84Asn	missense	Exon 3 of 7	ENSP00000594343.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251486

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111714

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.81

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0033

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

PhyloP100

0.73

PrimateAI

Benign

0.44

REVEL

Benign

0.060

Sift4G

Benign

0.38

Vest4

0.38

MVP

0.072

MPC

0.54

ClinPred

0.062

GERP RS

1.1

Varity_R

0.10

gMVP

0.28

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over