11-67452097-C-G

Variant names:

• chr11-67452097-C-G
• rs540353236
• NM_206997.1:c.628G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206997.1(GPR152):​c.628G>C​(p.Val210Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR152 NM_206997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10539603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR152	NM_206997.1	c.628G>C	p.Val210Leu	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.628G>C	p.Val210Leu	missense_variant	Exon 1 of 1	6	NM_206997.1	ENSP00000310255.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246432 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133958

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459698 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.3
DANN	Benign	0.94
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.048
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		0.031	B
Vest4		0.12
MutPred		0.63		Loss of helix (P = 0.1706);
MVP		0.30
MPC		0.28
ClinPred		0.044	T
GERP RS		1.4
Varity_R		0.083
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs540353236; hg19: chr11-67219568;