Genetic Variant GPR101:p.Ala419Ser (chrX-137030420-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_054021.2(GPR101):c.1255G>T(p.Ala419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,097,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 0 hem. )

Consequence

GPR101
NM_054021.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27937382).

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.1255G>T	p.Ala419Ser	missense	Exon 2 of 2	NP_473362.1	Q96P66

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR101	ENST00000651716.2	MANE Select	c.1255G>T	p.Ala419Ser	missense	Exon 2 of 2	ENSP00000498972.1	Q96P66
ENSG00000291054	ENST00000693626.3		n.404-30105C>A		intron	N/A
ENSG00000291054	ENST00000759385.1		n.500-30105C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

182638

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1097957

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363319

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.00

AC:

AN:

35190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19356

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40519

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000713

AC:

AN:

842003

Other (OTH)

AF:

0.00

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.56

M_CAP

Benign

0.0088

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

2.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.31

Sift4G

Benign

0.36

Polyphen

0.89

Vest4

0.35

MutPred

0.70

Loss of catalytic residue at A419 (P = 0.0187)

MVP

0.84

MPC

1.3

ClinPred

0.33

GERP RS

4.9

Varity_R

0.31

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over