Genetic Variant GPR26:p.Ala24Val (chr10-123666478-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153442.4(GPR26):c.71C>T(p.Ala24Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,408,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPR26
NM_153442.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.86

Publications

0 publications found

Variant links:

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]

GPR26 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09098178).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153442.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR26	NM_153442.4	MANE Select	c.71C>T	p.Ala24Val	missense	Exon 1 of 3	NP_703143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR26	ENST00000284674.2	TSL:1 MANE Select	c.71C>T	p.Ala24Val	missense	Exon 1 of 3	ENSP00000284674.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1408124

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697374

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31744

American (AMR)

AF:

0.00

AC:

AN:

38862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.00

AC:

AN:

36792

South Asian (SAS)

AF:

0.00

AC:

AN:

80316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4408

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091356

Other (OTH)

AF:

0.0000171

AC:

AN:

58508

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.013

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.096

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

3.9

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.69

REVEL

Benign

0.14

Sift

Benign

0.98

Sift4G

Benign

1.0

Polyphen

0.011

Vest4

0.12

MutPred

0.65

Gain of helix (P = 0.0854)

MVP

0.16

MPC

0.94

ClinPred

0.51

GERP RS

1.4

PromoterAI

0.0088

Neutral

(source)

Varity_R

0.030

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over