Variant chr9-33261138-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004323.6(BAG1):c.612G>C(p.Leu204Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BAG1
NM_004323.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.236

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]

BAG1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG1	NM_004323.6 linkuse as main transcript	c.612G>C	p.Leu204Phe	missense_variant	3/7	ENST00000634734.3	NP_004314.6	Q99933-1
BAG1	NM_001349286.2 linkuse as main transcript	c.399G>C	p.Leu133Phe	missense_variant	3/7		NP_001336215.1
BAG1	NM_001172415.2 linkuse as main transcript	c.267G>C	p.Leu89Phe	missense_variant	3/7		NP_001165886.1	Q99933-4
BAG1	NM_001349299.2 linkuse as main transcript	c.198G>C	p.Leu66Phe	missense_variant	3/7		NP_001336228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG1	ENST00000634734.3 linkuse as main transcript	c.612G>C	p.Leu204Phe	missense_variant	3/7	1	NM_004323.6	ENSP00000489189.2		Q99933-1J3QTA2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458168

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jun 27, 2022

The c.612G>C (p.L204F) alteration is located in exon 3 (coding exon 3) of the BAG1 gene. This alteration results from a G to C substitution at nucleotide position 612, causing the leucine (L) at amino acid position 204 to be replaced by a phenylalanine (F). 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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

.;.;D;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.79

D;D;D;D

MetaSVM

Uncertain

0.60

MutationAssessor

Pathogenic

3.7

.;.;H;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.5

.;D;.;D

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0050

.;D;.;D

Sift4G

Benign

0.11

T;D;.;.

Polyphen

1.0

.;.;D;.

Vest4

0.91

MutPred

0.68

Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);.;

MVP

0.74

ClinPred

0.99

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.75

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over