Variant 19-48956242-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138761.4(BAX):c.278T>C(p.Phe93Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BAX
NM_138761.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAX	NM_138761.4 linkuse as main transcript	c.278T>C	p.Phe93Ser	missense_variant	4/6	ENST00000345358.12	NP_620116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAX	ENST00000345358.12 linkuse as main transcript	c.278T>C	p.Phe93Ser	missense_variant	4/6	1	NM_138761.4	ENSP00000263262	P1	Q07812-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1440220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716260

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.278T>C (p.F93S) alteration is located in exon 4 (coding exon 4) of the BAX gene. This alteration results from a T to C substitution at nucleotide position 278, causing the phenylalanine (F) at amino acid position 93 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T;.;.;T;.

Eigen

Benign

0.095

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.63

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

N;.;N;.;.;N

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.4

D;.;D;D;.;D

REVEL

Benign

0.26

Sift

Benign

0.046

D;.;D;T;.;T

Sift4G

Benign

0.43

T;T;T;T;T;T

Polyphen

0.80

P;.;B;B;.;B

Vest4

0.79

MutPred

0.52

Gain of disorder (P = 0.0076);.;Gain of disorder (P = 0.0076);.;.;Gain of disorder (P = 0.0076);

MVP

0.53

MPC

0.68

ClinPred

0.84

GERP RS

4.0

Varity_R

0.78

gMVP

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over