X-137030519-T-G

Position:

• chrX-137030519-T-G

Variant summary

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

The NM_054021.2(GPR101):​c.1156A>C​(p.Asn386His) 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: GPR101 NM_054021.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.57

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051305354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR101	NM_054021.2	c.1156A>C	p.Asn386His	missense_variant	2/2	ENST00000651716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR101	ENST00000651716.2	c.1156A>C	p.Asn386His	missense_variant	2/2		NM_054021.2	P1
	ENST00000693626.2	n.394-30006T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Richard Lifton Laboratory, Yale University School of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.62
DEOGEN2	Benign	0.0018	T
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.077
Sift	Benign	0.18	T
Sift4G	Benign	0.12	T
Polyphen		0.0020	B
Vest4		0.082
MutPred		0.37		Loss of helix (P = 0.1299);
MVP		0.87
MPC		0.49
ClinPred		0.061	T
GERP RS		-2.5
Varity_R		0.071

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: rs386352311; hg19: chrX-136112678;