6-31640679-A-T

Position:

• chr6-31640679-A-T

Variant summary

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

The NM_001387994.1(BAG6):​c.2960T>A​(p.Val987Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BAG6 NM_001387994.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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]

BAG6 (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=0.12804669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.2960T>A	p.Val987Asp	missense_variant	22/26	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.2960T>A	p.Val987Asp	missense_variant	22/26		NM_001387994.1	ENSP00000502941.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.2870T>A (p.V957D) alteration is located in exon 21 (coding exon 20) of the BAG6 gene. This alteration results from a T to A substitution at nucleotide position 2870, causing the valine (V) at amino acid position 957 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.12	.;.;T;.;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;.;N;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.94	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.047	D;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;D
Polyphen		0.023	B;B;B;.;.
Vest4		0.26
MutPred		0.16		.;.;Gain of relative solvent accessibility (P = 0.0082);.;.;
MVP		0.57
MPC		0.95
ClinPred		0.53	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.80

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: chr6-31608456;