14-103559907-A-C

Variant names:

• chr14-103559907-A-C
• NM_001015048.3:c.1258T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001015048.3(BAG5):​c.1258T>G​(p.Cys420Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15

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 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
BAG5	NM_001015048.3	c.1258T>G	p.Cys420Gly	missense_variant	Exon 2 of 2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.1258T>G	p.Cys420Gly	missense_variant	Exon 2 of 2		NP_001015049.2
BAG5	NM_004873.4	c.1258T>G	p.Cys420Gly	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.1258T>G	p.Cys420Gly	missense_variant	Exon 2 of 2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.1258T>G	p.Cys420Gly	missense_variant	Exon 2 of 2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.1258T>G	p.Cys420Gly	missense_variant	Exon 2 of 2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1860A>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727228

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.49	T;T;.
Eigen	Benign	0.064
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.092	T;T;T
Polyphen		0.059	B;B;B
Vest4		0.49
MutPred		0.73		Loss of methylation at K419 (P = 0.0152);Loss of methylation at K419 (P = 0.0152);.;
MVP		0.92
MPC		0.73
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.84
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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.

Other links and lift over

hg19: chr14-104026244;