Variant rs139111924 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_054021.2(GPR101):c.712G>A(p.Val238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,210,460 control chromosomes in the GnomAD database, including 59 homozygotes. There are 824 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 31 hom., 427 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 28 hom. 397 hem. )

Consequence

GPR101
NM_054021.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.18

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:

ENSG00000291054 (HGNC:):

ENSG00000291054 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023664832).

BP6

Variant X-137030963-C-T is Benign according to our data. Variant chrX-137030963-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1478/112423) while in subpopulation AFR AF= 0.045 (1390/30889). AF 95% confidence interval is 0.043. There are 31 homozygotes in gnomad4. There are 427 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR101	NM_054021.2 link	c.712G>A	p.Val238Ile	missense_variant	2/2	ENST00000651716.2	NP_473362.1	Q96P66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR101	ENST00000651716.2 link	c.712G>A	p.Val238Ile	missense_variant	2/2		NM_054021.2	ENSP00000498972.1		Q96P66
ENSG00000291054	ENST00000693626.2 link	n.394-29562C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1461

AN:

112370

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

413

AN XY:

34526

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00553

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000741

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.0132

GnomAD3 exomes

AF:

0.00375

AC:

687

AN:

183316

Hom.:

AF XY:

0.00260

AC XY:

176

AN XY:

67758

show subpopulations

Gnomad AFR exome

AF:

0.0461

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00137

AC:

1503

AN:

1098037

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

397

AN XY:

363393

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.00382

GnomAD4 genome

AF:

0.0131

AC:

1478

AN:

112423

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

427

AN XY:

34589

show subpopulations

Gnomad4 AFR

AF:

0.0450

Gnomad4 AMR

AF:

0.00552

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000743

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.0131

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.0157

ESP6500AA

AF:

0.0459

AC:

176

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00434

AC:

527

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 04, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.2

DANN

Benign

0.54

DEOGEN2

Benign

0.0037

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.070

REVEL

Benign

0.089

Sift

Benign

0.41

Sift4G

Benign

0.48

Polyphen

0.32

Vest4

0.031

MVP

0.54

MPC

0.46

ClinPred

0.014

GERP RS

4.4

Varity_R

0.046

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

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