chr11-67452373-C-A

Variant names:

• chr11-67452373-C-A
• rs148000171
• NM_206997.1:c.352G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206997.1(GPR152):​c.352G>T​(p.Gly118Cys) 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 1,460,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G118S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR152 NM_206997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• 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]

CABP4 (HGNC:1386): (calcium binding protein 4) This gene encodes a member of the CABP family of calcium binding protein characterized by four EF-hand motifs. Mutations in this gene are associated with congenital stationary night blindness type 2B. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CABP4 Gene-Disease associations (from GenCC):

• cone-rod synaptic disorder, congenital nonprogressive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

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.352G>T	p.Gly118Cys	missense	Exon 1 of 1	NP_996880.1	Q8TDT2
	CABP4	NM_001300896.3		c.-386C>A		upstream_gene	N/A	NP_001287825.1	P57796-2
	CABP4	NM_001379183.1		c.-782C>A		upstream_gene	N/A	NP_001366112.1	P57796-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR152	ENST00000312457.2	TSL:6 MANE Select	c.352G>T	p.Gly118Cys	missense	Exon 1 of 1	ENSP00000310255.2	Q8TDT2
	CABP4	ENST00000438189.6	TSL:1	c.-386C>A		upstream_gene	N/A	ENSP00000401555.2	P57796-2
	CABP4	ENST00000545040.1	TSL:1	n.-63C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726460

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

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52166

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111762

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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.54
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.81		Loss of glycosylation at S117 (P = 0.0459)
MVP		0.67
MPC		0.99
ClinPred		0.98	D
GERP RS		4.9
PromoterAI		-0.11	Neutral
Varity_R		0.31
gMVP		0.58
Mutation Taster		=81/19	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: rs148000171; hg19: chr11-67219844;