chr4-850940-A-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005255.4(GAK):c.3653T>G(p.Leu1218Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,612,172 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0061 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 15 hom. )
Consequence
GAK
NM_005255.4 missense
NM_005255.4 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 9.11
Genes affected
GAK (HGNC:4113): (cyclin G associated kinase) In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008222342).
BP6
?
Variant 4-850940-A-C is Benign according to our data. Variant chr4-850940-A-C is described in ClinVar as [Benign]. Clinvar id is 720325.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00605 (921/152178) while in subpopulation AFR AF= 0.0211 (877/41532). AF 95% confidence interval is 0.02. There are 11 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 922 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAK | NM_005255.4 | c.3653T>G | p.Leu1218Arg | missense_variant | 26/28 | ENST00000314167.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAK | ENST00000314167.9 | c.3653T>G | p.Leu1218Arg | missense_variant | 26/28 | 1 | NM_005255.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00606 AC: 922AN: 152060Hom.: 11 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00170 AC: 426AN: 250762Hom.: 12 AF XY: 0.00120 AC XY: 163AN XY: 135578
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GnomAD4 exome AF: 0.000629 AC: 918AN: 1459994Hom.: 15 Cov.: 30 AF XY: 0.000512 AC XY: 372AN XY: 726200
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GnomAD4 genome ? AF: 0.00605 AC: 921AN: 152178Hom.: 11 Cov.: 32 AF XY: 0.00567 AC XY: 422AN XY: 74398
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258
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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