Variant X-41727965-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_080817.5(GPR82):c.939T>C(p.Asp313Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.80 ( 25439 hom., 26333 hem., cov: 23)

Exomes 𝑓: 0.79 ( 224617 hom. 262596 hem. )

Failed GnomAD Quality Control

Consequence

GPR82
NM_080817.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.628

Variant links:

Genes affected

GPR82 (HGNC:4533): (G protein-coupled receptor 82) 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]

GPR82 links:

CASK (HGNC:1497): (calcium/calmodulin dependent serine protein kinase) This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

CASK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-41727965-T-C is Benign according to our data. Variant chrX-41727965-T-C is described in ClinVar as [Benign]. Clinvar id is 158075.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.628 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR82	NM_080817.5 link	c.939T>C	p.Asp313Asp	synonymous_variant	3/3	ENST00000302548.5	NP_543007.1	Q96P67
CASK	NM_001367721.1 link	c.429+11419A>G		intron_variant		ENST00000378163.7	NP_001354650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR82	ENST00000302548.5 link	c.939T>C	p.Asp313Asp	synonymous_variant	3/3	1	NM_080817.5	ENSP00000303549.4		Q96P67
CASK	ENST00000378163.7 link	c.429+11419A>G		intron_variant		5	NM_001367721.1	ENSP00000367405.1		O14936-1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

88973

AN:

110677

Hom.:

25439

Cov.:

AF XY:

0.799

AC XY:

26291

AN XY:

32901

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.858

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.717

Gnomad NFE

AF:

0.769

Gnomad OTH

AF:

0.789

GnomAD3 exomes

AF:

0.812

AC:

140928

AN:

173634

Hom.:

37984

AF XY:

0.812

AC XY:

48605

AN XY:

59866

show subpopulations

Gnomad AFR exome

AF:

0.870

Gnomad AMR exome

AF:

0.907

Gnomad ASJ exome

AF:

0.679

Gnomad EAS exome

AF:

0.990

Gnomad SAS exome

AF:

0.867

Gnomad FIN exome

AF:

0.682

Gnomad NFE exome

AF:

0.767

Gnomad OTH exome

AF:

0.789

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.788

AC:

831839

AN:

1055742

Hom.:

224617

Cov.:

AF XY:

0.795

AC XY:

262596

AN XY:

330312

show subpopulations

Gnomad4 AFR exome

AF:

0.870

Gnomad4 AMR exome

AF:

0.904

Gnomad4 ASJ exome

AF:

0.684

Gnomad4 EAS exome

AF:

0.974

Gnomad4 SAS exome

AF:

0.861

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.777

Gnomad4 OTH exome

AF:

0.793

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.804

AC:

89010

AN:

110728

Hom.:

25439

Cov.:

AF XY:

0.799

AC XY:

26333

AN XY:

32962

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.686

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.859

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.769

Gnomad4 OTH

AF:

0.793

Alfa

AF:

0.777

Hom.:

44917

Bravo

AF:

0.821

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.8

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over