NM_004323.6:c.547G>T

Variant names:

• chr9-33262735-C-A
• rs565441106
• NM_004323.6:c.547G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004323.6(BAG1):​c.547G>T​(p.Val183Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V183I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAG1 NM_004323.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG1	NM_004323.6	c.547G>T	p.Val183Phe	missense_variant	Exon 2 of 7	ENST00000634734.3	NP_004314.6
BAG1	NM_001349286.2	c.334G>T	p.Val112Phe	missense_variant	Exon 2 of 7		NP_001336215.1
BAG1	NM_001172415.2	c.202G>T	p.Val68Phe	missense_variant	Exon 2 of 7		NP_001165886.1
BAG1	NM_001349299.2	c.133G>T	p.Val45Phe	missense_variant	Exon 2 of 7		NP_001336228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG1	ENST00000634734.3	c.547G>T	p.Val183Phe	missense_variant	Exon 2 of 7	1	NM_004323.6	ENSP00000489189.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249248 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	.;.;D;T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	0.0064	D
MutationAssessor	Pathogenic	3.3	.;.;M;.;.
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.5	.;D;.;D;.
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0020	.;D;.;D;.
Sift4G	Uncertain	0.029	D;D;.;.;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.85
MutPred		0.45		Gain of helix (P = 0.0861);.;Gain of helix (P = 0.0861);.;.;
MVP		0.71
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.83
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs565441106; hg19: chr9-33262733;