chrX-137030751-C-G

Position:

chrX-137030751-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_054021.2(GPR101):c.924G>C(p.Glu308Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,209,166 control chromosomes in the GnomAD database, including 15 homozygotes. There are 1,903 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E308E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., 91 hem., cov: 22)

Exomes 𝑓: 0.0049 ( 14 hom. 1812 hem. )

Consequence

GPR101
NM_054021.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:4O:1

Conservation

PhyloP100: -1.90

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004725307).

BP6

Variant X-137030751-C-G is Benign according to our data. Variant chrX-137030751-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 167871.We mark this variant Likely_benign, oryginal submissions are: {not_provided=1, Likely_benign=1, Uncertain_significance=1}. Variant chrX-137030751-C-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 91 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR101	NM_054021.2 linkuse as main transcript	c.924G>C	p.Glu308Asp	missense_variant	2/2	ENST00000651716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR101	ENST00000651716.2 linkuse as main transcript	c.924G>C	p.Glu308Asp	missense_variant	2/2		NM_054021.2	P1
	ENST00000693626.2 linkuse as main transcript	n.394-29774C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

382

AN:

110993

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

AN XY:

33195

show subpopulations

Gnomad AFR

AF:

0.000690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00104

Gnomad ASJ

AF:

0.00949

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00117

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00571

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.00353

AC:

647

AN:

183283

Hom.:

AF XY:

0.00365

AC XY:

247

AN XY:

67727

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00485

GnomAD4 exome

AF:

0.00489

AC:

5368

AN:

1098119

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

1812

AN XY:

363479

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.00882

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.00418

Gnomad4 NFE exome

AF:

0.00557

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00344

AC:

382

AN:

111047

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

AN XY:

33259

show subpopulations

Gnomad4 AFR

AF:

0.000688

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00949

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00117

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.00571

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00450

AC:

ExAC

AF:

0.00360

AC:

437

EpiCase

AF:

0.00545

EpiControl

AF:

0.00486

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:4Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Pituitary adenoma, growth hormone-secreting, 2

Pathogenic:1Uncertain:1Other:1

Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 26, 2015	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

GPR101-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 03, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.19

DANN

Benign

0.41

DEOGEN2

Benign

0.0026

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.53

REVEL

Benign

0.028

Sift

Benign

0.13

Sift4G

Benign

0.068

Polyphen

0.0010

Vest4

0.033

MutPred

0.18

Gain of glycosylation at S309 (P = 0.1215);

MVP

0.51

MPC

0.43

ClinPred

0.0029

GERP RS

-5.2

Varity_R

0.057

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over