9-33264320-T-C

Variant summary

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

The NM_004323.6(BAG1):​c.355A>G​(p.Ser119Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

BAG1
NM_004323.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.20

Publications

0 publications found
Variant links:
Genes affected
BAG1 (HGNC:937): (BAG cochaperone 1) The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X. [provided by RefSeq, Feb 2010]

Genome browser will be placed here

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=0.051418096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BAG1NM_004323.6 linkc.355A>G p.Ser119Gly missense_variant Exon 1 of 7 ENST00000634734.3 NP_004314.6 Q99933-1
BAG1NM_001349286.2 linkc.142A>G p.Ser48Gly missense_variant Exon 1 of 7 NP_001336215.1
BAG1NM_001172415.2 linkc.10A>G p.Ser4Gly missense_variant Exon 1 of 7 NP_001165886.1 Q99933-4
BAG1NM_001349299.2 linkc.-60A>G 5_prime_UTR_variant Exon 1 of 7 NP_001336228.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BAG1ENST00000634734.3 linkc.355A>G p.Ser119Gly missense_variant Exon 1 of 7 1 NM_004323.6 ENSP00000489189.2 Q99933-1J3QTA2

Frequencies

GnomAD3 genomes
AF:
0.00000665
AC:
1
AN:
150332
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000196
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
GnomAD2 exomes
AF:
0.0000159
AC:
4
AN:
251322
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:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461814
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727216
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53384
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111984
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
AF:
0.00000665
AC:
1
AN:
150332
Hom.:
0
Cov.:
31
AF XY:
0.0000136
AC XY:
1
AN XY:
73390
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40712
American (AMR)
AF:
0.00
AC:
0
AN:
15162
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3450
East Asian (EAS)
AF:
0.000196
AC:
1
AN:
5104
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4690
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10426
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67508
Other (OTH)
AF:
0.00
AC:
0
AN:
2060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 20, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.355A>G (p.S119G) alteration is located in exon 1 (coding exon 1) of the BAG1 gene. This alteration results from a A to G substitution at nucleotide position 355, causing the serine (S) at amino acid position 119 to be replaced by a glycine (G). 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
0.090
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
13
DANN
Benign
0.97
DEOGEN2
Benign
0.27
.;.;T;T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.36
T;T;T;T;T;.
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.051
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;.;M;.;.;.
PhyloP100
-1.2
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.75
.;N;.;N;.;D
REVEL
Benign
0.0030
Sift
Benign
0.21
.;T;.;T;.;.
Sift4G
Benign
0.27
T;T;.;.;T;.
Polyphen
0.0
.;.;B;.;.;.
Vest4
0.14
MutPred
0.18
Loss of phosphorylation at S119 (P = 0.0088);.;Loss of phosphorylation at S119 (P = 0.0088);.;.;.;
MVP
0.11
ClinPred
0.037
T
GERP RS
0.51
PromoterAI
-0.014
Neutral
Varity_R
0.025
gMVP
0.23
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs1294373376; hg19: chr9-33264318; API