chr11-67452018-G-A

Variant names:

• chr11-67452018-G-A
• rs371595474
• NM_206997.1:c.707C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206997.1(GPR152):​c.707C>T​(p.Ala236Val) 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 1,459,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. A236D) has been classified as Uncertain significance.

• 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: 0.448
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0953154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206997.1. 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
	GPR152	NM_206997.1	MANE Select	c.707C>T	p.Ala236Val	missense	Exon 1 of 1	NP_996880.1	Q8TDT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR152	ENST00000312457.2	TSL:6 MANE Select	c.707C>T	p.Ala236Val	missense	Exon 1 of 1	ENSP00000310255.2	Q8TDT2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459656 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726200

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.45
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.10
Sift	Benign	0.32	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.13	B
Vest4		0.17
MutPred		0.56		Gain of MoRF binding (P = 0.111)
MVP		0.65
MPC		0.94
ClinPred		0.32	T
GERP RS		3.7
PromoterAI		-0.0089	Neutral
Varity_R		0.085
gMVP		0.18
Mutation Taster		=97/3	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: rs371595474; hg19: chr11-67219489;