11-67452000-A-C

Variant names:

• chr11-67452000-A-C
• NM_206997.1:c.725T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206997.1(GPR152):​c.725T>G​(p.Ile242Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR152 NM_206997.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.976

Genes affected

GPR152 (HGNC:23622): (G protein-coupled receptor 152) Enables identical protein binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR152	NM_206997.1	c.725T>G	p.Ile242Ser	missense_variant	Exon 1 of 1	ENST00000312457.2	NP_996880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR152	ENST00000312457.2	c.725T>G	p.Ile242Ser	missense_variant	Exon 1 of 1	6	NM_206997.1	ENSP00000310255.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.725T>G (p.I242S) alteration is located in exon 1 (coding exon 1) of the GPR152 gene. This alteration results from a T to G substitution at nucleotide position 725, causing the isoleucine (I) at amino acid position 242 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	0.020
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.92	P
Vest4		0.57
MutPred		0.76		Loss of helix (P = 0.079);
MVP		0.66
MPC		1.1
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.79
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67219471;