X-137030381-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_054021.2(GPR101):​c.1294C>T​(p.Pro432Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,208,041 control chromosomes in the GnomAD database, including 1 homozygotes. There are 81 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., 39 hem., cov: 23)
Exomes 𝑓: 0.00013 ( 0 hom. 42 hem. )

Consequence

GPR101
NM_054021.2 missense

Scores

2
7
8

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013741642).
BP6
Variant X-137030381-G-A is Benign according to our data. Variant chrX-137030381-G-A is described in ClinVar as [Benign]. Clinvar id is 1590841.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR101NM_054021.2 linkuse as main transcriptc.1294C>T p.Pro432Ser missense_variant 2/2 ENST00000651716.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR101ENST00000651716.2 linkuse as main transcriptc.1294C>T p.Pro432Ser missense_variant 2/2 NM_054021.2 P1
ENST00000693626.2 linkuse as main transcriptn.394-30144G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00134
AC:
150
AN:
111588
Hom.:
1
Cov.:
23
AF XY:
0.00116
AC XY:
39
AN XY:
33764
show subpopulations
Gnomad AFR
AF:
0.00467
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000378
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00417
Gnomad NFE
AF:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000305
AC:
55
AN:
180188
Hom.:
0
AF XY:
0.0000926
AC XY:
6
AN XY:
64800
show subpopulations
Gnomad AFR exome
AF:
0.00380
Gnomad AMR exome
AF:
0.000147
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:
0.00
Gnomad OTH exome
AF:
0.000224
GnomAD4 exome
AF:
0.000132
AC:
145
AN:
1096399
Hom.:
0
Cov.:
31
AF XY:
0.000116
AC XY:
42
AN XY:
361889
show subpopulations
Gnomad4 AFR exome
AF:
0.00440
Gnomad4 AMR exome
AF:
0.000142
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000594
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.00133
AC:
149
AN:
111642
Hom.:
1
Cov.:
23
AF XY:
0.00115
AC XY:
39
AN XY:
33828
show subpopulations
Gnomad4 AFR
AF:
0.00463
Gnomad4 AMR
AF:
0.000378
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000180
Hom.:
5
Bravo
AF:
0.00144
ESP6500AA
AF:
0.00365
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000329
AC:
40

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 16, 2024- -
GPR101-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 28, 2023This 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
Pathogenic
0.74
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.014
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.33
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.022
D
Polyphen
1.0
D
Vest4
0.54
MVP
0.95
MPC
1.4
ClinPred
0.090
T
GERP RS
5.3
Varity_R
0.32

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.

Other links and lift over

dbSNP: rs114879480; hg19: chrX-136112540; API