NM_001387994.1:c.2643G>T

Variant names:

• chr6-31641339-C-A
• rs142878083
• NM_001387994.1:c.2643G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001387994.1(BAG6):​c.2643G>T​(p.Ala881Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A881A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: BAG6 NM_001387994.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=-0.53 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	NM_001387994.1	MANE Select	c.2643G>T	p.Ala881Ala	synonymous	Exon 19 of 26	NP_001374923.1	P46379-3
	BAG6	NM_001388012.1		c.2670G>T	p.Ala890Ala	synonymous	Exon 19 of 26	NP_001374941.1
	BAG6	NM_001387989.1		c.2643G>T	p.Ala881Ala	synonymous	Exon 19 of 26	NP_001374918.1	P46379-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG6	ENST00000676615.2	MANE Select	c.2643G>T	p.Ala881Ala	synonymous	Exon 19 of 26	ENSP00000502941.1	P46379-3
	BAG6	ENST00000211379.9	TSL:1	c.2535G>T	p.Ala845Ala	synonymous	Exon 18 of 25	ENSP00000211379.5	P46379-2
	BAG6	ENST00000375976.8	TSL:1	c.2535G>T	p.Ala845Ala	synonymous	Exon 18 of 25	ENSP00000365143.4	P46379-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461848 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		-0.53
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs142878083; hg19: chr6-31609116;