14-103560576-G-C

Variant names:

• chr14-103560576-G-C
• NM_001015048.3:c.589C>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.589C>G​(p.Arg197Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892

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, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.589C>G	p.Arg197Gly	missense_variant	Exon 2 of 2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.589C>G	p.Arg197Gly	missense_variant	Exon 2 of 2		NP_001015049.2
BAG5	NM_004873.4	c.589C>G	p.Arg197Gly	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.589C>G	p.Arg197Gly	missense_variant	Exon 2 of 2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.589C>G	p.Arg197Gly	missense_variant	Exon 2 of 2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.589C>G	p.Arg197Gly	missense_variant	Exon 2 of 2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1191G>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

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: 8.99e-7

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	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D;.;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	-0.033	T
MutationAssessor	Benign	1.0	L;L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;.
Polyphen		0.90	P;P;P;.
Vest4		0.83
MutPred		0.77		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;Gain of loop (P = 0.0312);
MVP		0.96
MPC		0.88
ClinPred		0.82	D
GERP RS		-1.7
Varity_R		0.62
gMVP		0.64

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.

Other links and lift over

hg19: chr14-104026913;