rs2229730
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_004383.3(CSK):c.759C>T(p.Gly253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,613,282 control chromosomes in the GnomAD database, including 8,203 homozygotes. 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 0.064 ( 631 hom., cov: 33)
Exomes 𝑓: 0.064 ( 7572 hom. )
Consequence
CSK
NM_004383.3 synonymous
NM_004383.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.66
Genes affected
CSK (HGNC:2444): (C-terminal Src kinase) The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
?
Synonymous conserved (PhyloP=-2.66 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSK | NM_004383.3 | c.759C>T | p.Gly253= | synonymous_variant | 9/13 | ENST00000220003.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSK | ENST00000220003.14 | c.759C>T | p.Gly253= | synonymous_variant | 9/13 | 1 | NM_004383.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0638 AC: 9697AN: 152070Hom.: 628 Cov.: 33
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GnomAD3 exomes AF: 0.105 AC: 26406AN: 251010Hom.: 2864 AF XY: 0.113 AC XY: 15373AN XY: 135828
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GnomAD4 exome AF: 0.0643 AC: 93917AN: 1461094Hom.: 7572 Cov.: 33 AF XY: 0.0718 AC XY: 52210AN XY: 726866
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GnomAD4 genome ? AF: 0.0638 AC: 9716AN: 152188Hom.: 631 Cov.: 33 AF XY: 0.0714 AC XY: 5314AN XY: 74422
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Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at