rs139111924

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/19 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

Publications

2 publications found

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 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

GPR101 links:

ENSG00000291054 (HGNC:):

ENSG00000291054 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR101	NM_054021.2 link	c.712G>A	p.Val238Ile	missense_variant	Exon 2 of 2	ENST00000651716.2	NP_473362.1	Q96P66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR101	ENST00000651716.2 link	c.712G>A	p.Val238Ile	missense_variant	Exon 2 of 2		NM_054021.2	ENSP00000498972.1		Q96P66

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1461

AN:

112370

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00375

AC:

687

AN:

183316

AF XY:

0.00260

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 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

African (AFR)

AF:

0.0447

AC:

1181

AN:

26397

American (AMR)

AF:

0.00287

AC:

101

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000129

AC:

AN:

54144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40508

Middle Eastern (MID)

AF:

0.00169

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000368

AC:

AN:

841964

Other (OTH)

AF:

0.00382

AC:

176

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0131

AC:

1478

AN:

112423

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

427

AN XY:

34589

show subpopulations

African (AFR)

AF:

0.0450

AC:

1390

AN:

30889

American (AMR)

AF:

0.00552

AC:

AN:

10681

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3590

South Asian (SAS)

AF:

0.000743

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000131

AC:

AN:

53307

Other (OTH)

AF:

0.0131

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

105

157

210

262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00426

Hom.:

192

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

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

1.2

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over