14-103560454-T-G

Position:

chr14-103560454-T-G

Variant summary

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

The NM_001015048.3(BAG5):c.711A>C(p.Glu237Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BAG5
NM_001015048.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

BAG5 (HGNC:941): (BAG cochaperone 5) The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions through interactions with a variety of cell apoptosis and growth related proteins including BCL-2, Raf-protein kinase, steroid hormone receptors, growth factor receptors and members of the heat shock protein 70 kDa family. This protein contains a BAG domain near the C-terminus, which could bind and inhibit the chaperone activity of Hsc70/Hsp70. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BAG5 links:

ENSG00000258851 (HGNC:):

ENSG00000258851 links:

Genome browser will be placed here

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=0.08405116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG5	NM_001015048.3 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2	ENST00000299204.6	NP_001015048.1	Q9UL15-1A0A024R6M6
BAG5	NM_001015049.5 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2		NP_001015049.2	Q9UL15-1A0A024R6M6
BAG5	NM_004873.4 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2		NP_004864.1	Q9UL15-1A0A024R6M6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BAG5	ENST00000299204.6 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2	1	NM_001015048.3	ENSP00000299204.4	Q9UL15-1
BAG5	ENST00000337322.5 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2	1		ENSP00000338814.5	Q9UL15-1
BAG5	ENST00000445922.2 linkuse as main transcript	c.711A>C	p.Glu237Asp	missense_variant	2/2	1		ENSP00000391713.2	Q9UL15-1
ENSG00000258851	ENST00000556332.1 linkuse as main transcript	n.443-1313T>G		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

The c.834A>C (p.E278D) alteration is located in exon 2 (coding exon 2) of the BAG5 gene. This alteration results from a A to C substitution at nucleotide position 834, causing the glutamic acid (E) at amino acid position 278 to be replaced by an aspartic acid (D). 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

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.52

DANN

Benign

0.96

DEOGEN2

Benign

0.30

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.77

T;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.55

N;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.088

MutPred

0.49

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;

MVP

0.63

MPC

0.20

ClinPred

0.26

GERP RS

-7.2

Varity_R

0.042

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