X-41727580-GC-AT

Variant names:

• chrX-41727580-GC-AT
• NM_080817.5:c.554_555delGCinsAT
• GPR82 p.Ser185Asn

Variant summary

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

The NM_080817.5(GPR82):​c.554_555delGCinsAT​(p.Ser185Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPR82 NM_080817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 0 publications found

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]

CASK Gene-Disease associations (from GenCC):

• FG syndrome 4

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• syndromic X-linked intellectual disability Najm type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080817.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR82	NM_080817.5	MANE Select	c.554_555delGCinsAT	p.Ser185Asn	missense	N/A	NP_543007.1	Q96P67
	CASK	NM_001367721.1	MANE Select	c.429+11803_429+11804delGCinsAT		intron	N/A	NP_001354650.1	O14936-1
	CASK	NM_003688.4		c.429+11803_429+11804delGCinsAT		intron	N/A	NP_003679.2	O14936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR82	ENST00000302548.5	TSL:1 MANE Select	c.554_555delGCinsAT	p.Ser185Asn	missense	N/A	ENSP00000303549.4	Q96P67
	CASK	ENST00000378163.7	TSL:5 MANE Select	c.429+11803_429+11804delGCinsAT		intron	N/A	ENSP00000367405.1	O14936-1
	CASK	ENST00000421587.8	TSL:1	c.447+11803_447+11804delGCinsAT		intron	N/A	ENSP00000400526.4	A0A7I2RJN6

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-41586833;