10-123666522-C-G

Position:

• chr10-123666522-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153442.4(GPR26):​c.115C>G​(p.Gln39Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GPR26 NM_153442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

Genes affected

GPR26 (HGNC:4481): (G protein-coupled receptor 26) This gene encodes a G protein-couple receptor protein. G-protein-coupled receptors are a large family of membrane proteins that are involved in cellular responses to environmental stimuli, neurotransmitters, and hormones. The encoded protein may play a role in neurodegenerative diseases. Epigenetic silencing of this gene has been observed in gliomas. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR26	NM_153442.4	c.115C>G	p.Gln39Glu	missense_variant	1/3	ENST00000284674.2	NP_703143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR26	ENST00000284674.2	c.115C>G	p.Gln39Glu	missense_variant	1/3	1	NM_153442.4	ENSP00000284674.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.115C>G (p.Q39E) alteration is located in exon 1 (coding exon 1) of the GPR26 gene. This alteration results from a C to G substitution at nucleotide position 115, causing the glutamine (Q) at amino acid position 39 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.19
Sift	Benign	0.035	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.58		Loss of helix (P = 0.0626);
MVP		0.61
MPC		2.1
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.26
gMVP		0.77

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: chr10-125426038;