chr11-125627771-G-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001114122.3(CHEK1):c.230G>T(p.Gly77Val) variant causes a missense change. The variant allele was found at a frequency of 0.000187 in 1,612,834 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0013 ( 4 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 1 hom. )
Consequence
CHEK1
NM_001114122.3 missense
NM_001114122.3 missense
Scores
3
4
8
Clinical Significance
Conservation
PhyloP100: 7.13
Genes affected
CHEK1 (HGNC:1925): (checkpoint kinase 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.027391374).
BS2
High AC in GnomAd4 at 194 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK1 | NM_001114122.3 | c.230G>T | p.Gly77Val | missense_variant | 3/13 | ENST00000438015.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK1 | ENST00000438015.7 | c.230G>T | p.Gly77Val | missense_variant | 3/13 | 5 | NM_001114122.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00127 AC: 194AN: 152178Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000386 AC: 97AN: 251008Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135722
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1460656Hom.: 1 Cov.: 31 AF XY: 0.0000688 AC XY: 50AN XY: 726662
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GnomAD4 genome AF: 0.00127 AC: 194AN: 152178Hom.: 4 Cov.: 32 AF XY: 0.00195 AC XY: 145AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.230G>T (p.G77V) alteration is located in exon 3 (coding exon 2) of the CHEK1 gene. This alteration results from a G to T substitution at nucleotide position 230, causing the glycine (G) at amino acid position 77 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;D;D;.;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.;L;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T
Polyphen
0.84
.;P;P;.;.;.;P;P;.;.
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);
MVP
MPC
1.4
ClinPred
T
GERP RS
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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