chrX-41531460-T-G

Position:

• chrX-41531460-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367721.1(CASK):​c.2318-251A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 110,711 control chromosomes in the GnomAD database, including 8,677 homozygotes. There are 14,843 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (8677 hom., 14843 hem., cov: 22)
• Consequence: CASK NM_001367721.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.761

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-41531460-T-G is Benign according to our data. Variant chrX-41531460-T-G is described in ClinVar as [Benign]. Clinvar id is 668060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASK	NM_001367721.1	c.2318-251A>C		intron_variant		ENST00000378163.7	NP_001354650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASK	ENST00000378163.7	c.2318-251A>C		intron_variant		5	NM_001367721.1	ENSP00000367405.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 50644 AN: 110659 Hom.: 8669 Cov.: 22 AF XY: 0.450 AC XY: 14814 AN XY: 32907

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.458 AC: 50680 AN: 110711 Hom.: 8677 Cov.: 22 AF XY: 0.450 AC XY: 14843 AN XY: 32969

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.477

Alfa AF: 0.440 Hom.: 34536

Bravo AF: 0.485

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.72

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: rs2998250; hg19: chrX-41390713;