NM_023915.4:c.729G>C

Variant names:

• chr3-151294517-C-G
• NM_023915.4:c.729G>C

Variant summary

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

The NM_023915.4(GPR87):​c.729G>C​(p.Gln243His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR87 NM_023915.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

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]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286273 (HGNC:):

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=0.11951044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023915.4. 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
	GPR87	NM_023915.4	MANE Select	c.729G>C	p.Gln243His	missense	Exon 3 of 3	NP_076404.3
	MED12L	NM_001393769.1	MANE Select	c.2251-55542C>G		intron	N/A	NP_001380698.1	A0A8I5KX78
	MED12L	NM_053002.6		c.2146-55542C>G		intron	N/A	NP_443728.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR87	ENST00000260843.5	TSL:1 MANE Select	c.729G>C	p.Gln243His	missense	Exon 3 of 3	ENSP00000260843.4	Q9BY21
	MED12L	ENST00000687756.1	MANE Select	c.2251-55542C>G		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	MED12L	ENST00000474524.5	TSL:1	c.2146-55542C>G		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.0048
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.23
Sift	Benign	0.18	T
Sift4G	Benign	0.14	T
Polyphen		0.97	D
Vest4		0.17
MutPred		0.29		Gain of glycosylation at S245 (P = 0.0086)
MVP		0.81
MPC		0.21
ClinPred		0.41	T
GERP RS		2.6
Varity_R		0.048
gMVP		0.37
Mutation Taster		=88/12	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

hg19: chr3-151012305;