Variant 10-119672255-C-G 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_004281.4(BAG3):c.508C>G(p.Arg170Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R170Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

BAG3
NM_004281.4 missense, splice_region

Scores

Splicing: ADA: 0.004641

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

BAG3 (HGNC:939): (BAG cochaperone 3) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

BAG3 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=0.14497405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG3	NM_004281.4 linkuse as main transcript	c.508C>G	p.Arg170Gly	missense_variant, splice_region_variant	3/4	ENST00000369085.8	NP_004272.2	O95817
BAG3	XM_005270287.2 linkuse as main transcript	c.508C>G	p.Arg170Gly	missense_variant, splice_region_variant	3/4		XP_005270344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG3	ENST00000369085.8 linkuse as main transcript	c.508C>G	p.Arg170Gly	missense_variant, splice_region_variant	3/4	1	NM_004281.4	ENSP00000358081.4		O95817
BAG3	ENST00000450186.1 linkuse as main transcript	c.334C>G	p.Arg112Gly	missense_variant, splice_region_variant	4/5	5		ENSP00000410036.1		C9JFK9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246670

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134218

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.20

Sift

Benign

0.31

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.041

B;.

Vest4

0.36

MutPred

0.13

Gain of glycosylation at S171 (P = 0.1082);.;

MVP

0.85

MPC

0.41

ClinPred

0.55

GERP RS

3.1

Varity_R

0.12

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0046

dbscSNV1_RF

Benign

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over