14-103559873-G-T

Variant names:

• chr14-103559873-G-T
• rs754086545
• NM_001015048.3:c.1292C>A

Variant summary

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

The NM_001015048.3(BAG5):​c.1292C>A​(p.Ala431Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18

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, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.1292C>A	p.Ala431Glu	missense_variant	Exon 2 of 2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.1292C>A	p.Ala431Glu	missense_variant	Exon 2 of 2		NP_001015049.2
BAG5	NM_004873.4	c.1292C>A	p.Ala431Glu	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.1292C>A	p.Ala431Glu	missense_variant	Exon 2 of 2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.1292C>A	p.Ala431Glu	missense_variant	Exon 2 of 2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.1292C>A	p.Ala431Glu	missense_variant	Exon 2 of 2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1894G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;D;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.78	N;N;N
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0070	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.95
MutPred		0.72		Loss of MoRF binding (P = 0.0379);Loss of MoRF binding (P = 0.0379);.;
MVP		0.95
MPC		0.87
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.64
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs754086545; hg19: chr14-104026210;