rs1052486

Positions:

• chr6-31642909-A-C
• chr6-31642909-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387994.1(BAG6):​c.1963T>G​(p.Ser655Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BAG6 NM_001387994.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560

Genes affected

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033126265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.1963T>G	p.Ser655Ala	missense_variant	15/26	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.1963T>G	p.Ser655Ala	missense_variant	15/26		NM_001387994.1	ENSP00000502941	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458070 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 725082

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: 0.00

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	0.054
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.074	.;.;T;.;.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.46	N
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.033	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.76	.;.;N;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.20	N;N;N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.87	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;.;T
Polyphen		0.0	B;B;B;.;.;.
Vest4		0.069
MutPred		0.18		.;.;Loss of glycosylation at S625 (P = 5e-04);.;.;.;
MVP		0.25
MPC		0.34
ClinPred		0.072	T
GERP RS		3.7
Varity_R		0.040
gMVP		0.18

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: rs1052486; hg19: chr6-31610686;