Variant 6-36317376-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001010903.5(BNIP5):c.1939A>G(p.Lys647Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

BNIP5
NM_001010903.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00400

Variant links:

Genes affected

BNIP5 (HGNC:33769): (BCL2 interacting protein 5)

BNIP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026972681).

BP6

Variant 6-36317376-T-C is Benign according to our data. Variant chr6-36317376-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3134677.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP5	NM_001010903.5 linkuse as main transcript	c.1939A>G	p.Lys647Glu	missense_variant	12/12	ENST00000437635.3	NP_001010903.3
BNIP5	XM_011514596.3 linkuse as main transcript	c.1939A>G	p.Lys647Glu	missense_variant	12/12		XP_011512898.1	P0C671
BNIP5	XM_011514597.3 linkuse as main transcript	c.1936A>G	p.Lys646Glu	missense_variant	12/12		XP_011512899.1
BNIP5	XM_011514598.3 linkuse as main transcript	c.1195A>G	p.Lys399Glu	missense_variant	11/11		XP_011512900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP5	ENST00000437635.3 linkuse as main transcript	c.1939A>G	p.Lys647Glu	missense_variant	12/12	1	NM_001010903.5	ENSP00000418983.1		P0C671

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248854

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134700

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461212

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.3

DANN

Benign

0.13

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00074

LIST_S2

Benign

0.19

M_CAP

Benign

0.0023

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PROVEAN

Benign

1.3

REVEL

Benign

0.039

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MutPred

0.19

Loss of ubiquitination at K647 (P = 2e-04);

MVP

0.030

MPC

0.013

ClinPred

0.025

GERP RS

1.2

Varity_R

0.053

gMVP

0.020

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