6-33575916-G-T

Variant names:

• chr6-33575916-G-T
• NM_001188.4:c.83C>A

Variant summary

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

The NM_001188.4(BAK1):​c.83C>A​(p.Ala28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A28V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BAK1 NM_001188.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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]

GGNBP1 (HGNC:19427): (gametogenetin binding protein 1 (pseudogene)) This gene is the ortholog of the mouse gametogenetin-binding protein 1 gene. In human, the open reading frame is disrupted by a nonsense mutation after 8-aa; consequently, this gene is currently considered to be a unitary pseudogene in human even though it is functional in other mammals. [provided by RefSeq, Aug 2009]

ACMG classification

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 rank	MANE	Protein	UniProt
BAK1	NM_001188.4	c.83C>A	p.Ala28Asp	missense_variant	Exon 3 of 6	ENST00000374467.4	NP_001179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAK1	ENST00000374467.4	c.83C>A	p.Ala28Asp	missense_variant	Exon 3 of 6	1	NM_001188.4	ENSP00000363591.3
BAK1	ENST00000442998.6	c.83C>A	p.Ala28Asp	missense_variant	Exon 3 of 7	1		ENSP00000391258.2
GGNBP1	ENST00000612409.1	n.362+452G>T		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;.;T
Eigen	Benign	0.065
Eigen_PC	Benign	-0.0049
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.0069	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D;D
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.81	.;.;P
Vest4		0.66
MutPred		0.16		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.75
MPC		0.70
ClinPred		0.93	D
GERP RS		0.77
Varity_R		0.65
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-33543693;