NM_054021.2:c.1465G>C

Variant names:

• chrX-137030210-C-G
• rs760719928
• NM_054021.2:c.1465G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054021.2(GPR101):​c.1465G>C​(p.Gly489Arg) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPR101 NM_054021.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.317
• Publications: 2 publications found

Genes affected

GPR101 (HGNC:14963): (G protein-coupled receptor 101) The protein encoded by this gene is an orphan G protein-coupled receptor of unknown function. The encoded protein is a member of a family of proteins that contain seven transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. [provided by RefSeq, Sep 2011]

GPR101 Gene-Disease associations (from GenCC):

• pituitary adenoma, growth hormone-secreting, 2

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• acromegaly

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000291054 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06606078).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054021.2. 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
	GPR101	NM_054021.2	MANE Select	c.1465G>C	p.Gly489Arg	missense	Exon 2 of 2	NP_473362.1	Q96P66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR101	ENST00000651716.2	MANE Select	c.1465G>C	p.Gly489Arg	missense	Exon 2 of 2	ENSP00000498972.1	Q96P66
	ENSG00000291054	ENST00000693626.3		n.404-30315C>G		intron	N/A
	ENSG00000291054	ENST00000759385.1		n.500-30315C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.15
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0021	T
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.32
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.065
Sift	Uncertain	0.021	D
Sift4G	Benign	0.15	T
Polyphen		0.31	B
Vest4		0.078
MutPred		0.17		Loss of glycosylation at T490 (P = 0.0603)
MVP		0.43
MPC		1.5
ClinPred		0.33	T
GERP RS		3.4
Varity_R		0.062
Mutation Taster		=98/2	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: rs760719928; hg19: chrX-136112369; COSMIC: COSV53240052;