rs929319102

Variant names:

• chr19-48961065-G-A
• rs929319102
• ENST00000293288.12:c.625G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48961065-G-A
• chr19-48961065-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004324.4(BAX):​c.625G>A​(p.Val209Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,260 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (1 hom.)
• Consequence: BAX NM_004324.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.177
• Publications: 1 publications found

Genes affected

BAX (HGNC:959): (BCL2 associated X, apoptosis regulator) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Dec 2019]

BAX Gene-Disease associations (from GenCC):

• leukemia, acute lymphocytic, susceptibility to, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000305635 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077660054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004324.4. 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
	BAX	NM_138761.4	MANE Select	c.474+151G>A		intron	N/A	NP_620116.1	Q07812-1
	BAX	NM_004324.4		c.625G>A	p.Val209Met	missense	Exon 5 of 5	NP_004315.1	Q07812-2
	BAX	NM_001291429.2		c.514G>A	p.Val172Met	missense	Exon 4 of 4	NP_001278358.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAX	ENST00000293288.12	TSL:1	c.625G>A	p.Val209Met	missense	Exon 5 of 5	ENSP00000293288.8	Q07812-2
	BAX	ENST00000539787.2	TSL:1	c.391G>A	p.Val131Met	missense	Exon 3 of 3	ENSP00000441413.2	I6LPK7
	BAX	ENST00000345358.12	TSL:1 MANE Select	c.474+151G>A		intron	N/A	ENSP00000263262.9	Q07812-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241664 AF XY: 0.00000758

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1456260 Hom.: 1 Cov.: 35 AF XY: 0.00000414 AC XY: 3 AN XY: 724572

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111280

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.1
DANN	Benign	0.89
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.18
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.010
Sift	Pathogenic	0.0	D
Polyphen		0.0070	B
Vest4		0.15
MutPred		0.27		Loss of sheet (P = 0.0126)
MVP		0.37
MPC		0.18
ClinPred		0.10	T
GERP RS		-0.41
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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: rs929319102; hg19: chr19-49464322;