chr6-31642909-A-T

Variant names:

• chr6-31642909-A-T
• rs1052486
• NM_001387994.1:c.1963T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388012.1(BAG6):​c.1990T>A​(p.Ser664Thr) 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. 16/22 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_001388012.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041493714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388012.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	NM_001387994.1	MANE Select	c.1963T>A	p.Ser655Thr	missense	Exon 15 of 26	NP_001374923.1
	BAG6	NM_001388012.1		c.1990T>A	p.Ser664Thr	missense	Exon 15 of 26	NP_001374941.1
	BAG6	NM_001387989.1		c.1963T>A	p.Ser655Thr	missense	Exon 15 of 26	NP_001374918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	ENST00000676615.2	MANE Select	c.1963T>A	p.Ser655Thr	missense	Exon 15 of 26	ENSP00000502941.1
	BAG6	ENST00000211379.9	TSL:1	c.1855T>A	p.Ser619Thr	missense	Exon 14 of 25	ENSP00000211379.5
	BAG6	ENST00000375976.8	TSL:1	c.1855T>A	p.Ser619Thr	missense	Exon 14 of 25	ENSP00000365143.4

Frequencies

GnomAD3 genomes Cov.: 32

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

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00 AC: 0 AN: 85698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110432

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.56
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.053
Sift	Benign	0.51	T
Sift4G	Benign	0.53	T
Polyphen		0.0010	B
Vest4		0.080
MutPred		0.17		Loss of glycosylation at S625 (P = 0.0472)
MVP		0.25
MPC		0.37
ClinPred		0.092	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.19
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1052486; hg19: chr6-31610686;