X-41727965-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_080817.5(GPR82):c.939T>C(p.Asp313=) 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 Likely benign (no stars).

• 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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.628

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 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 [Likely_benign]. Clinvar id is 158075.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.628 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 25439 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR82	NM_080817.5	c.939T>C	p.Asp313=	synonymous_variant	3/3	ENST00000302548.5
CASK	NM_001367721.1	c.429+11419A>G		intron_variant		ENST00000378163.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR82	ENST00000302548.5	c.939T>C	p.Asp313=	synonymous_variant	3/3	1	NM_080817.5	P1
CASK	ENST00000378163.7	c.429+11419A>G		intron_variant		5	NM_001367721.1	A1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 88973 AN: 110677 Hom.: 25439 Cov.: 23 AF XY: 0.799 AC XY: 26291 AN XY: 32901

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

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.: 22 AF XY: 0.795 AC XY: 262596 AN XY: 330312

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.: 23 AF XY: 0.799 AC XY: 26333 AN XY: 32962

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: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

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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

Other links and lift over

dbSNP: rs1023065; hg19: chrX-41587218;