chrX-41520450-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001367721.1(CASK):c.2751A>G(p.Pro917=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 111,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.000027 ( 0 hom., 1 hem., cov: 22)
Consequence
CASK
NM_001367721.1 synonymous
NM_001367721.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.81
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant X-41520450-T-C is Benign according to our data. Variant chrX-41520450-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2189274.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.81 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.2751A>G | p.Pro917= | synonymous_variant | 27/27 | ENST00000378163.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASK | ENST00000378163.7 | c.2751A>G | p.Pro917= | synonymous_variant | 27/27 | 5 | NM_001367721.1 | A1 | |
CASK-AS1 | ENST00000451126.1 | n.331+84T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111586Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33760
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GnomAD4 exome Cov.: 29
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GnomAD4 genome ? AF: 0.0000269 AC: 3AN: 111643Hom.: 0 Cov.: 22 AF XY: 0.0000296 AC XY: 1AN XY: 33827
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, CASK-related, X-linked Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2022 | - - |
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