14-103561073-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001015048.3(BAG5):c.92G>C(p.Ser31Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00188 in 1,611,370 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (10 hom.)
• Consequence: BAG5 NM_001015048.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.88

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024344355).
• BP6: Variant 14-103561073-C-G is Benign according to our data. Variant chr14-103561073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3234177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAG5	NM_001015048.3	c.92G>C	p.Ser31Thr	missense_variant	2/2	ENST00000299204.6
BAG5	NM_001015049.5	c.92G>C	p.Ser31Thr	missense_variant	2/2
BAG5	NM_004873.4	c.92G>C	p.Ser31Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAG5	ENST00000299204.6	c.92G>C	p.Ser31Thr	missense_variant	2/2	1	NM_001015048.3	P1
BAG5	ENST00000337322.5	c.92G>C	p.Ser31Thr	missense_variant	2/2	1		P1
BAG5	ENST00000445922.2	c.92G>C	p.Ser31Thr	missense_variant	2/2	1		P1
	ENST00000556332.1	n.443-694C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00152 AC: 379 AN: 249276 Hom.: 2 AF XY: 0.00167 AC XY: 226 AN XY: 135030

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00212

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00195 AC: 2849 AN: 1459064 Hom.: 10 Cov.: 31 AF XY: 0.00202 AC XY: 1470 AN XY: 726040

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00241

Gnomad4 FIN exome AF: 0.00122

Gnomad4 NFE exome AF: 0.00218

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00121 AC: 185 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00118 AC XY: 88 AN XY: 74476

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.00176

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00114

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00158 AC: 192

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00225

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

BAG5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T;.;.
Eigen	Benign	0.090
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;.;T;T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.024	T;T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.9	L;L;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.76	N;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Uncertain	0.058	T;T;T;.
Polyphen		0.46	P;P;P;.
Vest4		0.44
MVP		0.94
MPC		0.66
ClinPred		0.043	T
GERP RS		3.0
Varity_R		0.23
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs143718197; hg19: chr14-104027410;