11-125627740-GTA-TTG

Variant names:

• chr11-125627740-GTA-TTG
• NM_001114122.3:c.199_201delGTAinsTTG
• CHEK1 p.Val67Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001114122.3(CHEK1):​c.199_201delGTAinsTTG​(p.Val67Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V67I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHEK1 NM_001114122.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45
• Publications: 0 publications found

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]

CHEK1 Gene-Disease associations (from GenCC):

• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHEK1	NM_001114122.3	MANE Select	c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	NP_001107594.1	O14757-1
	CHEK1	NM_001114121.2		c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	NP_001107593.1	O14757-1
	CHEK1	NM_001274.5		c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	NP_001265.2	O14757-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHEK1	ENST00000438015.7	TSL:5 MANE Select	c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	ENSP00000388648.1	O14757-1
	CHEK1	ENST00000428830.6	TSL:1	c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	ENSP00000412504.2	O14757-1
	CHEK1	ENST00000534070.5	TSL:1	c.199_201delGTAinsTTG	p.Val67Leu	missense	N/A	ENSP00000435371.1	O14757-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-125497635;