rs41431245
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001367721.1(CASK):āc.363T>Cā(p.Tyr121=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0041 in 1,148,328 control chromosomes in the GnomAD database, including 71 homozygotes. There are 1,456 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0066 ( 9 hom., 264 hem., cov: 23)
Exomes š: 0.0038 ( 62 hom. 1192 hem. )
Consequence
CASK
NM_001367721.1 synonymous
NM_001367721.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.43
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant X-41739450-A-G is Benign according to our data. Variant chrX-41739450-A-G is described in ClinVar as [Benign]. Clinvar id is 94378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-41739450-A-G is described in Lovd as [Likely_benign].
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.363T>C | p.Tyr121= | synonymous_variant | 5/27 | ENST00000378163.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASK | ENST00000378163.7 | c.363T>C | p.Tyr121= | synonymous_variant | 5/27 | 5 | NM_001367721.1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00662 AC: 742AN: 112021Hom.: 8 Cov.: 23 AF XY: 0.00769 AC XY: 263AN XY: 34179
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GnomAD3 exomes AF: 0.0130 AC: 2365AN: 182555Hom.: 46 AF XY: 0.00976 AC XY: 655AN XY: 67145
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GnomAD4 exome AF: 0.00382 AC: 3958AN: 1036255Hom.: 62 Cov.: 22 AF XY: 0.00381 AC XY: 1192AN XY: 312817
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GnomAD4 genome AF: 0.00665 AC: 745AN: 112073Hom.: 9 Cov.: 23 AF XY: 0.00771 AC XY: 264AN XY: 34241
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 15, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Intellectual disability, CASK-related, X-linked Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at