rs143991107
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001367721.1(CASK):c.1794C>T(p.Asn598=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 1,206,876 control chromosomes in the GnomAD database, including 2 homozygotes. There are 271 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00069 ( 0 hom., 24 hem., cov: 23)
Exomes 𝑓: 0.00059 ( 2 hom. 247 hem. )
Consequence
CASK
NM_001367721.1 synonymous
NM_001367721.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 7.56
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=-0.47).
BP6
?
Variant X-41557044-G-A is Benign according to our data. Variant chrX-41557044-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 94375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-41557044-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000688 (77/111956) while in subpopulation NFE AF= 0.000508 (27/53193). AF 95% confidence interval is 0.000358. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 24 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.1794C>T | p.Asn598= | synonymous_variant | 19/27 | ENST00000378163.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASK | ENST00000378163.7 | c.1794C>T | p.Asn598= | synonymous_variant | 19/27 | 5 | NM_001367721.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000688 AC: 77AN: 111901Hom.: 0 Cov.: 23 AF XY: 0.000705 AC XY: 24AN XY: 34053
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GnomAD3 exomes AF: 0.000993 AC: 182AN: 183279Hom.: 1 AF XY: 0.000944 AC XY: 64AN XY: 67765
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GnomAD4 exome AF: 0.000593 AC: 649AN: 1094920Hom.: 2 Cov.: 28 AF XY: 0.000685 AC XY: 247AN XY: 360448
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GnomAD4 genome ? AF: 0.000688 AC: 77AN: 111956Hom.: 0 Cov.: 23 AF XY: 0.000703 AC XY: 24AN XY: 34118
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 19, 2016 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 30, 2017 | 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 | Aug 28, 2018 | - - |
CASK-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 23, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Intellectual disability, CASK-related, X-linked Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 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