chrX-137030249-C-T

Variant names:

• chrX-137030249-C-T
• NM_054021.2:c.1426G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_054021.2(GPR101):​c.1426G>A​(p.Glu476Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPR101 NM_054021.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.717

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023437917).
• BP6: Variant X-137030249-C-T is Benign according to our data. Variant chrX-137030249-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3855033.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR101	NM_054021.2	c.1426G>A	p.Glu476Lys	missense_variant	Exon 2 of 2	ENST00000651716.2	NP_473362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR101	ENST00000651716.2	c.1426G>A	p.Glu476Lys	missense_variant	Exon 2 of 2		NM_054021.2	ENSP00000498972.1
ENSG00000291054	ENST00000693626.2	n.394-30276C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 31, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.044
DANN	Benign	0.62
DEOGEN2	Benign	0.00071	T
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.63	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.0050
Sift	Benign	0.96	T
Sift4G	Benign	0.63	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.30		Gain of methylation at E476 (P = 0.0017);
MVP		0.60
MPC		0.53
ClinPred		0.026	T
GERP RS		-1.4
Varity_R		0.044

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-136112408; COSMIC: COSV53240612;