NM_001387994.1:c.1963T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387994.1(BAG6):​c.1963T>C​(p.Ser655Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,609,852 control chromosomes in the GnomAD database, including 192,892 homozygotes. 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: 𝑓 0.45 (16025 hom., cov: 32)
  • Exomes 𝑓: 0.49 (176867 hom.)
• Consequence: BAG6 NM_001387994.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 76 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.3527514E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387994.1. 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>C	p.Ser655Pro	missense	Exon 15 of 26	NP_001374923.1
	BAG6	NM_001388012.1		c.1990T>C	p.Ser664Pro	missense	Exon 15 of 26	NP_001374941.1
	BAG6	NM_001387989.1		c.1963T>C	p.Ser655Pro	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>C	p.Ser655Pro	missense	Exon 15 of 26	ENSP00000502941.1
	BAG6	ENST00000211379.9	TSL:1	c.1855T>C	p.Ser619Pro	missense	Exon 14 of 25	ENSP00000211379.5
	BAG6	ENST00000375976.8	TSL:1	c.1855T>C	p.Ser619Pro	missense	Exon 14 of 25	ENSP00000365143.4

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68381 AN: 151860 Hom.: 16006 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.507 AC: 123046 AN: 242662 AF XY: 0.517

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.509

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.596

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.489 AC: 713223 AN: 1457874 Hom.: 176867 Cov.: 68 AF XY: 0.495 AC XY: 358718 AN XY: 724972

African (AFR) AF: 0.333 AC: 11146 AN: 33430

American (AMR) AF: 0.509 AC: 22557 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 16004 AN: 26078

East Asian (EAS) AF: 0.582 AC: 23028 AN: 39544

South Asian (SAS) AF: 0.590 AC: 50562 AN: 85676

European-Finnish (FIN) AF: 0.382 AC: 20118 AN: 52600

Middle Eastern (MID) AF: 0.537 AC: 3093 AN: 5758

European-Non Finnish (NFE) AF: 0.484 AC: 537042 AN: 1110324

Other (OTH) AF: 0.493 AC: 29673 AN: 60186

GnomAD4 genome AF: 0.450 AC: 68444 AN: 151978 Hom.: 16025 Cov.: 32 AF XY: 0.450 AC XY: 33425 AN XY: 74290

African (AFR) AF: 0.338 AC: 14009 AN: 41442

American (AMR) AF: 0.499 AC: 7636 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3472

East Asian (EAS) AF: 0.607 AC: 3133 AN: 5160

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3968 AN: 10578

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33006 AN: 67912

Other (OTH) AF: 0.485 AC: 1021 AN: 2104

Alfa AF: 0.485 Hom.: 73922

Bravo AF: 0.452

TwinsUK AF: 0.491 AC: 1821

ALSPAC AF: 0.489 AC: 1886

ESP6500AA AF: 0.338 AC: 1491

ESP6500EA AF: 0.487 AC: 4184

ExAC AF: 0.499 AC: 60495

Asia WGS AF: 0.598 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.31
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.25	N
MetaRNN	Benign	0.000054	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.56
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.080
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.049
MPC		0.51
ClinPred		0.0053	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.17
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV52989339; COSMIC: COSV52989339;