chr14-103559946-G-C

Position:

• chr14-103559946-G-C

Variant summary

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

The NM_001015048.3(BAG5):​c.1219C>G​(p.Leu407Val) variant causes a missense change. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41

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, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.1219C>G	p.Leu407Val	missense_variant	2/2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.1219C>G	p.Leu407Val	missense_variant	2/2		NP_001015049.2
BAG5	NM_004873.4	c.1219C>G	p.Leu407Val	missense_variant	2/2		NP_004864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG5	ENST00000299204.6	c.1219C>G	p.Leu407Val	missense_variant	2/2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.1219C>G	p.Leu407Val	missense_variant	2/2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.1219C>G	p.Leu407Val	missense_variant	2/2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1821G>C		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.1342C>G (p.L448V) alteration is located in exon 2 (coding exon 2) of the BAG5 gene. This alteration results from a C to G substitution at nucleotide position 1342, causing the leucine (L) at amino acid position 448 to be replaced by a valine (V). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.2	M;M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.70
MutPred		0.67		Gain of ubiquitination at K404 (P = 0.1079);Gain of ubiquitination at K404 (P = 0.1079);.;
MVP		0.90
MPC		0.81
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.88
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: chr14-104026283;