chr11-64270237-C-T

Variant names:

• chr11-64270237-C-T
• rs750374497
• NM_032989.3:c.479G>A

Variant summary

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

The NM_032989.3(BAD):​c.479G>A​(p.Gly160Asp) 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. G160V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BAD NM_032989.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

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]

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAD	NM_032989.3	MANE Select	c.479G>A	p.Gly160Asp	missense	Exon 4 of 4	NP_116784.1	Q92934
	BAD	NM_004322.3		c.479G>A	p.Gly160Asp	missense	Exon 3 of 3	NP_004313.1	Q92934

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAD	ENST00000309032.8	TSL:1 MANE Select	c.479G>A	p.Gly160Asp	missense	Exon 4 of 4	ENSP00000309103.3	Q92934
	BAD	ENST00000394532.7	TSL:1	c.479G>A	p.Gly160Asp	missense	Exon 3 of 3	ENSP00000378040.3	Q92934
	GPR137	ENST00000546139.5	TSL:1	c.-422C>T		5_prime_UTR	Exon 1 of 5	ENSP00000445570.1	F5H234

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.49
MVP		0.89
MPC		1.2
ClinPred		0.99	D
GERP RS		5.2
PromoterAI		-0.044	Neutral
Varity_R		0.67
gMVP		0.035
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs750374497; hg19: chr11-64037709;