X-137030534-G-C

Variant names:

• chrX-137030534-G-C
• rs137929096
• NM_054021.2:c.1141C>G

Variant summary

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

The NM_054021.2(GPR101):​c.1141C>G​(p.Arg381Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,208,500 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 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. R381H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: GPR101 NM_054021.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1141C>G	p.Arg381Gly	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.1141C>G	p.Arg381Gly	missense	Exon 2 of 2	ENSP00000498972.1	Q96P66
	ENSG00000291054	ENST00000693626.3		n.404-29991G>C		intron	N/A
	ENSG00000291054	ENST00000759385.1		n.500-29991G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111154 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 181507 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1097346 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362744

African (AFR) AF: 0.0000379 AC: 1 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19303

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 53881

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841697

Other (OTH) AF: 0.00 AC: 0 AN: 46062

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111154 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33344

African (AFR) AF: 0.0000656 AC: 2 AN: 30498

American (AMR) AF: 0.00 AC: 0 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2563

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52951

Other (OTH) AF: 0.00 AC: 0 AN: 1495

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.077
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.041	D
Polyphen		0.55	P
Vest4		0.15
MutPred		0.44		Loss of stability (P = 0.0279)
MVP		0.77
MPC		1.3
ClinPred		0.64	D
GERP RS		3.5
Varity_R		0.19
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs137929096; hg19: chrX-136112693;