11-64284271-C-T

Variant names:

• chr11-64284271-C-T
• NM_032989.3:c.98G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_032989.3(BAD):​c.98G>A​(p.Gly33Asp) 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BAD NM_032989.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.141
• 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: 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=0.06843397).
• BP6: Variant 11-64284271-C-T is Benign according to our data. Variant chr11-64284271-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3816928.Status of the report is criteria_provided_single_submitter, 1 stars.

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.98G>A	p.Gly33Asp	missense	Exon 2 of 4	NP_116784.1	Q92934
	BAD	NM_004322.3		c.98G>A	p.Gly33Asp	missense	Exon 1 of 3	NP_004313.1	Q92934
	GPR137	NM_001378078.1		c.-15-2239C>T		intron	N/A	NP_001365007.1	Q96N19-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAD	ENST00000309032.8	TSL:1 MANE Select	c.98G>A	p.Gly33Asp	missense	Exon 2 of 4	ENSP00000309103.3	Q92934
	BAD	ENST00000394532.7	TSL:1	c.98G>A	p.Gly33Asp	missense	Exon 1 of 3	ENSP00000378040.3	Q92934
	GPR137	ENST00000546139.5	TSL:1	c.4-2239C>T		intron	N/A	ENSP00000445570.1	F5H234

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.2
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.14
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.036
Sift	Benign	0.41	T
Sift4G	Benign	0.21	T
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.54		Loss of glycosylation at S32 (P = 0.0553)
MVP		0.25
MPC		0.48
ClinPred		0.050	T
GERP RS		0.67
PromoterAI		-0.054	Neutral
Varity_R		0.068
gMVP		0.098
Mutation Taster		=98/2	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

hg19: chr11-64051743;