chrX-41714313-T-C

Position:

• chrX-41714313-T-C

Variant summary

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

The NM_001367721.1(CASK):​c.429+25071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 110,170 control chromosomes in the GnomAD database, including 9,630 homozygotes. There are 15,669 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 0.49 (9630 hom., 15669 hem., cov: 22)
• Consequence: CASK NM_001367721.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASK	NM_001367721.1	c.429+25071A>G		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+25071A>G		intron_variant		5	NM_001367721.1	ENSP00000367405.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 53668 AN: 110117 Hom.: 9625 Cov.: 22 AF XY: 0.482 AC XY: 15635 AN XY: 32413

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.435

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.487 AC: 53704 AN: 110170 Hom.: 9630 Cov.: 22 AF XY: 0.482 AC XY: 15669 AN XY: 32476

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.497

Alfa AF: 0.477 Hom.: 32049

Bravo AF: 0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.52

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: rs6609159; hg19: chrX-41573566;