X-137030539-C-T

Variant names:

• chrX-137030539-C-T
• rs889126954
• NM_054021.2:c.1136G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_054021.2(GPR101):​c.1136G>A​(p.Ser379Asn) 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. 15/20 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. S379T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR101 NM_054021.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2908367).

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.1136G>A	p.Ser379Asn	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.1136G>A	p.Ser379Asn	missense	Exon 2 of 2	ENSP00000498972.1	Q96P66
	ENSG00000291054	ENST00000693626.3		n.404-29986C>T		intron	N/A
	ENSG00000291054	ENST00000759385.1		n.500-29986C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181719 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

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 Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097471 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362897

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.0000284 AC: 1 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19299

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 53903

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841776

Other (OTH) AF: 0.00 AC: 0 AN: 46067

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.16
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.95	P
Vest4		0.13
MutPred		0.27		Loss of phosphorylation at S379 (P = 0.0096)
MVP		0.94
MPC		1.3
ClinPred		0.50	T
GERP RS		2.5
Varity_R		0.10
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: rs889126954; hg19: chrX-136112698;