chr3-151294474-C-T

Variant names:

• chr3-151294474-C-T
• rs1330770210
• NM_023915.4:c.772G>A

Variant summary

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

The NM_023915.4(GPR87):​c.772G>A​(p.Val258Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPR87 NM_023915.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

GPR87 (HGNC:4538): (G protein-coupled receptor 87) This gene encodes a G protein-coupled receptor and is located in a cluster of G protein-couple receptor genes on chromosome 3. The encoded protein has been shown to be overexpressed in lung squamous cell carcinoma (PMID:18057535) and regulated by p53 (PMID:19602589). [provided by RefSeq, Nov 2011]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

ENSG00000286273 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR87	NM_023915.4	c.772G>A	p.Val258Met	missense_variant	Exon 3 of 3	ENST00000260843.5	NP_076404.3
MED12L	NM_001393769.1	c.2251-55585C>T		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR87	ENST00000260843.5	c.772G>A	p.Val258Met	missense_variant	Exon 3 of 3	1	NM_023915.4	ENSP00000260843.4
MED12L	ENST00000687756.1	c.2251-55585C>T		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.772G>A (p.V258M) alteration is located in exon 3 (coding exon 2) of the GPR87 gene. This alteration results from a G to A substitution at nucleotide position 772, causing the valine (V) at amino acid position 258 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.39
Sift	Benign	0.24	T
Sift4G	Benign	0.56	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.62		Gain of helix (P = 0.0696);
MVP		0.71
MPC		0.27
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.19
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs1330770210; hg19: chr3-151012262;