rs1284615128

Variant names:

• chr14-103560233-T-C
• rs1284615128
• NM_001015048.3:c.932A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001015048.3(BAG5):​c.932A>G​(p.Gln311Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 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: 0.0000021 (0 hom.)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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]

ENSG00000258851 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.863

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2		NP_001015049.2
BAG5	NM_004873.4	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2		NP_004864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG5	ENST00000299204.6	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.932A>G	p.Gln311Arg	missense_variant	Exon 2 of 2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1534T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251394 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135900

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1055A>G (p.Q352R) alteration is located in exon 2 (coding exon 2) of the BAG5 gene. This alteration results from a A to G substitution at nucleotide position 1055, causing the glutamine (Q) at amino acid position 352 to be replaced by an arginine (R). 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	0.33
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.60	N;N;N
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.95	P;P;D
Vest4		0.75
MutPred		0.67		Gain of phosphorylation at T308 (P = 0.094);Gain of phosphorylation at T308 (P = 0.094);.;
MVP		0.93
MPC		0.84
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.48
gMVP		0.81

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

LitVar

Other links and lift over

dbSNP: rs1284615128; hg19: chr14-104026570;