rs200090506

Variant names:

• chr6-31639162-T-A
• rs200090506
• NM_001387994.1:c.3458A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31639162-T-A
• chr6-31639162-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001387994.1(BAG6):​c.3458A>T​(p.Asn1153Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1153S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BAG6 NM_001387994.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG6	NM_001387994.1	c.3458A>T	p.Asn1153Ile	missense_variant	Exon 26 of 26	ENST00000676615.2	NP_001374923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG6	ENST00000676615.2	c.3458A>T	p.Asn1153Ile	missense_variant	Exon 26 of 26		NM_001387994.1	ENSP00000502941.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	.;.;D;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.74	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.0	.;.;M;.;.
PhyloP100		3.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.3	D;D;D;D;D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.71
MutPred		0.28		.;.;Loss of solvent accessibility (P = 0.0576);.;.;
MVP		0.66
MPC		0.31
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.84
Mutation Taster		=51/49	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: rs200090506; hg19: chr6-31606939;