11-64270304-C-G

Variant names:

Variant summary

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

The NM_032989.3(BAD):c.412G>C(p.Ala138Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,424,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A138T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

BAD
NM_032989.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

1 publications found

Variant links:

Genes affected

BAD (HGNC:936): (BCL2 associated agonist of cell death) The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL (B-cell lymphoma-extra large) and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform. [provided by RefSeq, Dec 2019]

BAD links:

GPR137 (HGNC:24300): (G protein-coupled receptor 137) Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR137 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032989.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAD	NM_032989.3	MANE Select	c.412G>C	p.Ala138Pro	missense	Exon 4 of 4	NP_116784.1	Q92934
BAD	NM_004322.3		c.412G>C	p.Ala138Pro	missense	Exon 3 of 3	NP_004313.1	Q92934
GPR137	NM_001378078.1		c.-373C>G		upstream_gene	N/A	NP_001365007.1	Q96N19-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BAD	ENST00000309032.8	TSL:1 MANE Select	c.412G>C	p.Ala138Pro	missense	Exon 4 of 4	ENSP00000309103.3	Q92934
BAD	ENST00000394532.7	TSL:1	c.412G>C	p.Ala138Pro	missense	Exon 3 of 3	ENSP00000378040.3	Q92934
GPR137	ENST00000546139.5	TSL:1	c.-355C>G		5_prime_UTR	Exon 1 of 5	ENSP00000445570.1	F5H234

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000862

AC:

AN:

231902

AF XY:

0.00

show subpopulations

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:

0.0000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1424010

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

702620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32602

American (AMR)

AF:

0.00

AC:

AN:

41112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24208

East Asian (EAS)

AF:

0.00

AC:

AN:

39008

South Asian (SAS)

AF:

0.00

AC:

AN:

83120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.0000331

AC:

AN:

1087396

Other (OTH)

AF:

0.00

AC:

AN:

58562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.8

PhyloP100

1.5

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.36

MutPred

0.68

Gain of glycosylation at A138 (P = 0.0351)

MVP

0.88

MPC

0.56

ClinPred

0.99

GERP RS

5.7

PromoterAI

-0.0051

Neutral

(source)

Varity_R

0.91

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over