Variant 9-123035204-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005294.3(GPR21):c.638A>T(p.Asn213Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GPR21
NM_005294.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

Variant links:

Genes affected

GPR21 (HGNC:4476): (G protein-coupled receptor 21) This gene encodes a member of the G-protein-coupled receptor 1 family. G-protein coupled receptors are membrane proteins which activate signaling cascades as a response to extracellular stress. The encoded protein activates a Gq signal transduction pathway which mobilizes calcium. [provided by RefSeq, Nov 2012]

GPR21 links:

RABGAP1 (HGNC:17155): (RAB GTPase activating protein 1) Enables GTPase activator activity and small GTPase binding activity. Involved in regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RABGAP1 links:

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ACMG classification

Classification made for transcript

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	UniProt
GPR21	NM_005294.3 linkuse as main transcript	c.638A>T	p.Asn213Ile	missense_variant	2/2	ENST00000616002.3
RABGAP1	NM_012197.4 linkuse as main transcript	c.1794+14745A>T		intron_variant		ENST00000373647.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR21	ENST00000616002.3 linkuse as main transcript	c.638A>T	p.Asn213Ile	missense_variant	2/2	1	NM_005294.3	P1
RABGAP1	ENST00000373647.9 linkuse as main transcript	c.1794+14745A>T		intron_variant		1	NM_012197.4	P1	Q9Y3P9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.638A>T (p.N213I) alteration is located in exon 1 (coding exon 1) of the GPR21 gene. This alteration results from a A to T substitution at nucleotide position 638, causing the asparagine (N) at amino acid position 213 to be replaced by an isoleucine (I). 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

Uncertain

0.49

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.94

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.27

Sift

Benign

0.036

.;D

Sift4G

Benign

0.080

T;T

Polyphen

0.94

.;P

Vest4

0.72

MutPred

0.65

Loss of catalytic residue at N213 (P = 0.1152);Loss of catalytic residue at N213 (P = 0.1152);

MVP

0.23

MPC

0.77

ClinPred

0.99

GERP RS

4.5

Varity_R

0.52

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over