6-33575844-A-G

Variant names:

• chr6-33575844-A-G
• rs1051912
• NM_001188.4:c.155T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001188.4(BAK1):​c.155T>C​(p.Val52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
• Consequence: BAK1 NM_001188.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 4 publications found

Genes affected

BAK1 (HGNC:949): (BCL2 antagonist/killer 1) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. [provided by RefSeq, Jul 2008]

ENSG00000293518 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016540289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001188.4. 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
	BAK1	NM_001188.4	MANE Select	c.155T>C	p.Val52Ala	missense	Exon 3 of 6	NP_001179.1	Q16611-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAK1	ENST00000374467.4	TSL:1 MANE Select	c.155T>C	p.Val52Ala	missense	Exon 3 of 6	ENSP00000363591.3	Q16611-1
	BAK1	ENST00000442998.6	TSL:1	c.155T>C	p.Val52Ala	missense	Exon 3 of 7	ENSP00000391258.2	Q16611-2
	BAK1	ENST00000938018.1		c.155T>C	p.Val52Ala	missense	Exon 3 of 6	ENSP00000608077.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.18
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.052	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.2	N
PhyloP100		-0.020
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.031
MutPred		0.29		Loss of loop (P = 0.0022)
MVP		0.085
MPC		0.47
ClinPred		0.029	T
GERP RS		1.8
Varity_R		0.098
gMVP		0.26
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1051912; hg19: chr6-33543621;