14-103560198-C-T

Variant names:

• chr14-103560198-C-T
• NM_001015048.3:c.967G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001015048.3(BAG5):​c.967G>A​(p.Glu323Lys) 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. In-silico tool predicts a benign 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: 5.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23593038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.967G>A	p.Glu323Lys	missense_variant	Exon 2 of 2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.967G>A	p.Glu323Lys	missense_variant	Exon 2 of 2		NP_001015049.2
BAG5	NM_004873.4	c.967G>A	p.Glu323Lys	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.967G>A	p.Glu323Lys	missense_variant	Exon 2 of 2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.967G>A	p.Glu323Lys	missense_variant	Exon 2 of 2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.967G>A	p.Glu323Lys	missense_variant	Exon 2 of 2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1569C>T		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: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

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	0.21
BayesDel_addAF	Benign	0.0047	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Uncertain	-0.014	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.033	B;B;B
Vest4		0.14
MutPred		0.60		Gain of MoRF binding (P = 0.0205);Gain of MoRF binding (P = 0.0205);.;
MVP		0.98
MPC		0.31
ClinPred		0.44	T
GERP RS		4.7
Varity_R		0.14
gMVP		0.43

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: chr14-104026535; COSMIC: COSV99914779; COSMIC: COSV99914779;