1-6249730-G-C

Variant names:

• chr1-6249730-G-C
• NM_207370.4:c.1438C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207370.4(GPR153):​c.1438C>G​(p.Pro480Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 908,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P480L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: GPR153 NM_207370.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.920

Genes affected

GPR153 (HGNC:23618): (G protein-coupled receptor 153) This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04513681).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR153	NM_207370.4	c.1438C>G	p.Pro480Ala	missense_variant	Exon 6 of 6	ENST00000377893.3	NP_997253.2
GPR153	XM_011541434.4	c.1438C>G	p.Pro480Ala	missense_variant	Exon 6 of 6		XP_011539736.1
GPR153	XM_017001250.2	c.1438C>G	p.Pro480Ala	missense_variant	Exon 5 of 5		XP_016856739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR153	ENST00000377893.3	c.1438C>G	p.Pro480Ala	missense_variant	Exon 6 of 6	1	NM_207370.4	ENSP00000367125.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 908472 Hom.: 0 Cov.: 31 AF XY: 0.00000235 AC XY: 1 AN XY: 425528

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: 0.00000123

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.66
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	0.080	T
Polyphen		0.028	B
Vest4		0.091
MutPred		0.18		Loss of catalytic residue at P479 (P = 0.0131);
MVP		0.29
MPC		0.33
ClinPred		0.055	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.39

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: chr1-6309790;