14-103560015-G-T

Position:

• chr14-103560015-G-T

Variant summary

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

The NM_001015048.3(BAG5):​c.1150C>A​(p.Leu384Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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=0.23123088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG5	NM_001015048.3	c.1150C>A	p.Leu384Ile	missense_variant	2/2	ENST00000299204.6	NP_001015048.1
BAG5	NM_001015049.5	c.1150C>A	p.Leu384Ile	missense_variant	2/2		NP_001015049.2
BAG5	NM_004873.4	c.1150C>A	p.Leu384Ile	missense_variant	2/2		NP_004864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG5	ENST00000299204.6	c.1150C>A	p.Leu384Ile	missense_variant	2/2	1	NM_001015048.3	ENSP00000299204.4
BAG5	ENST00000337322.5	c.1150C>A	p.Leu384Ile	missense_variant	2/2	1		ENSP00000338814.5
BAG5	ENST00000445922.2	c.1150C>A	p.Leu384Ile	missense_variant	2/2	1		ENSP00000391713.2
ENSG00000258851	ENST00000556332.1	n.443-1752G>T		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Aug 27, 2024

The c.1273C>A (p.L425I) alteration is located in exon 2 (coding exon 2) of the BAG5 gene. This alteration results from a C to A substitution at nucleotide position 1273, causing the leucine (L) at amino acid position 425 to be replaced by an isoleucine (I). 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	Benign	0.099
BayesDel_addAF	Benign	-0.0031	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.41	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.041
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.42	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.14
MutPred		0.50		Loss of catalytic residue at L384 (P = 0.0778);Loss of catalytic residue at L384 (P = 0.0778);.;
MVP		0.88
MPC		0.25
ClinPred		0.43	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.095

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: chr14-104026352;