chr14-105051347-C-T

Variant names:

• chr14-105051347-C-T
• rs777838540
• NM_013345.4:c.790G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_013345.4(GPR132):​c.790G>A​(p.Val264Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V264F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: GPR132 NM_013345.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52
• Publications: 1 publications found

Genes affected

GPR132 (HGNC:17482): (G protein-coupled receptor 132) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein was reported to be a receptor for lysophosphatidylcholine action, but PubMedID: 15653487 retracts this finding and instead suggests this protein to be an effector of lysophosphatidylcholine action. This protein may have proton-sensing activity and may be a receptor for oxidized free fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

LINC02298 (HGNC:53216): (long intergenic non-protein coding RNA 2298)

LOC124903398 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020197958).
• BP6: Variant 14-105051347-C-T is Benign according to our data. Variant chr14-105051347-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3101397.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013345.4. 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
	GPR132	NM_013345.4	MANE Select	c.790G>A	p.Val264Ile	missense	Exon 4 of 4	NP_037477.1	Q9UNW8-1
	GPR132	NM_001278694.2		c.790G>A	p.Val264Ile	missense	Exon 5 of 5	NP_001265623.1	Q9UNW8-1
	GPR132	NM_001278695.2		c.763G>A	p.Val255Ile	missense	Exon 3 of 3	NP_001265624.1	Q9UNW8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR132	ENST00000329797.8	TSL:1 MANE Select	c.790G>A	p.Val264Ile	missense	Exon 4 of 4	ENSP00000328818.3	Q9UNW8-1
	GPR132	ENST00000392585.2	TSL:1	c.763G>A	p.Val255Ile	missense	Exon 3 of 3	ENSP00000376364.2	Q9UNW8-3
	GPR132	ENST00000551869.1	TSL:1	n.*816G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000448513.1	F8VRH8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251434 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461654 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000984 AC: 44 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111810

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.016
DANN	Benign	0.89
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.010	N
PhyloP100		-1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.016
Sift	Benign	0.57	T
Sift4G	Benign	0.78	T
Polyphen		0.051	B
Vest4		0.047
MutPred		0.41		Gain of catalytic residue at V261 (P = 0)
MVP		0.24
MPC		0.37
ClinPred		0.029	T
GERP RS		-7.6
Varity_R		0.025
gMVP		0.35
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs777838540; hg19: chr14-105517684; COSMIC: COSV61678110; COSMIC: COSV61678110;