X-41695561-T-C

Position:

• chrX-41695561-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001097579.2(GPR34):​c.-73T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (25454 hom., 25825 hem., cov: 22)
  • Exomes 𝑓: 0.79 (129675 hom. 131544 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR34 NM_001097579.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882

Genes affected

GPR34 (HGNC:4490): (G protein-coupled receptor 34) G protein-coupled receptors (GPCRs), such as GPR34, are integral membrane proteins containing 7 putative transmembrane domains (TMs). These proteins mediate signals to the interior of the cell via activation of heterotrimeric G proteins that in turn activate various effector proteins, ultimately resulting in a physiologic response.[supplied by OMIM, Apr 2006]

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR34	NM_001097579.2	c.-73T>C		5_prime_UTR_variant	3/3	ENST00000378142.9	NP_001091048.1
CASK	NM_001367721.1	c.430-24031A>G		intron_variant		ENST00000378163.7	NP_001354650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR34	ENST00000378142	c.-73T>C		5_prime_UTR_variant	3/3	1	NM_001097579.2	ENSP00000367384.4
CASK	ENST00000378163.7	c.430-24031A>G		intron_variant		5	NM_001367721.1	ENSP00000367405.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 88490 AN: 110011 Hom.: 25454 Cov.: 22 AF XY: 0.800 AC XY: 25786 AN XY: 32223

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.785

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.790 AC: 458612 AN: 580191 Hom.: 129675 Cov.: 9 AF XY: 0.799 AC XY: 131544 AN XY: 164693

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.897

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.804 AC: 88524 AN: 110058 Hom.: 25454 Cov.: 22 AF XY: 0.800 AC XY: 25825 AN XY: 32280

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.788

Alfa AF: 0.780 Hom.: 43543

Bravo AF: 0.822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.75

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: rs913602; hg19: chrX-41554814;