rs139111924

Positions:

• chrX-137030963-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.18

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]

ENSG00000291054 (HGNC:):

ACMG classification

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	c.712G>A	p.Val238Ile	missense_variant	2/2	ENST00000651716.2	NP_473362.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1461 AN: 112370 Hom.: 31 Cov.: 23 AF XY: 0.0120 AC XY: 413 AN XY: 34526

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.: 8 AF XY: 0.00260 AC XY: 176 AN XY: 67758

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.: 28 Cov.: 32 AF XY: 0.00109 AC XY: 397 AN XY: 363393

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.: 31 Cov.: 23 AF XY: 0.0123 AC XY: 427 AN XY: 34589

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.: 56

Bravo AF: 0.0157

ESP6500AA AF: 0.0459 AC: 176

ESP6500EA AF: 0.000149 AC: 1

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

Submissions by phenotype

not provided Benign:3

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.2
DANN	Benign	0.54
DEOGEN2	Benign	0.0037	T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.089
Sift	Benign	0.41	T
Sift4G	Benign	0.48	T
Polyphen		0.32	B
Vest4		0.031
MVP		0.54
MPC		0.46
ClinPred		0.014	T
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

Other links and lift over

dbSNP: rs139111924; hg19: chrX-136113122;