X-41730577-C-T

Position:

• chrX-41730577-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367721.1(CASK):​c.429+8807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 110,563 control chromosomes in the GnomAD database, including 5,741 homozygotes. There are 11,935 hemizygotes in GnomAD. 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 0.36 (5741 hom., 11935 hem., cov: 22)
• Consequence: CASK NM_001367721.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

Genes affected

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASK	NM_001367721.1	c.429+8807G>A		intron_variant		ENST00000378163.7	NP_001354650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASK	ENST00000378163.7	c.429+8807G>A		intron_variant		5	NM_001367721.1	ENSP00000367405.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 39669 AN: 110509 Hom.: 5743 Cov.: 22 AF XY: 0.364 AC XY: 11917 AN XY: 32725

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.359 AC: 39680 AN: 110563 Hom.: 5741 Cov.: 22 AF XY: 0.364 AC XY: 11935 AN XY: 32789

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.388

Alfa AF: 0.384 Hom.: 17776

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.77

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: rs4827286; hg19: chrX-41589830;