Variant 6-31643088-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001387994.1(BAG6):c.1784C>T(p.Pro595Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,581,872 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: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

BAG6
NM_001387994.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BAG6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, BAG6

BP4

Computational evidence support a benign effect (MetaRNN=0.18320143).

BS2

High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG6	NM_001387994.1 linkuse as main transcript	c.1784C>T	p.Pro595Leu	missense_variant	15/26	ENST00000676615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG6	ENST00000676615.2 linkuse as main transcript	c.1784C>T	p.Pro595Leu	missense_variant	15/26		NM_001387994.1	A2	P46379-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

194408

Hom.:

AF XY:

0.00000953

AC XY:

AN XY:

104894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000343

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000483

AC:

AN:

1429726

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

708538

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000236

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000527

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.00000842

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

Nov 29, 2023

The c.1694C>T (p.P565L) alteration is located in exon 14 (coding exon 13) of the BAG6 gene. This alteration results from a C to T substitution at nucleotide position 1694, causing the proline (P) at amino acid position 565 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.021

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.54

D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N;N;N;N;D

REVEL

Benign

0.069

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.034

D;D;D;D;.;D

Polyphen

1.0

D;D;D;.;.;.

Vest4

0.23

MutPred

0.26

.;.;Loss of glycosylation at P565 (P = 0.0016);.;.;.;

MVP

0.36

MPC

0.47

ClinPred

0.26

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.2

Varity_R

0.083

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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