NM_001826.3:c.33delA

Variant names:

• chr1-154974775-CA-C
• NM_001826.3:c.33delA

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001826.3(CKS1B):​c.33delA​(p.Lys11AsnfsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CKS1B NM_001826.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.52
• Publications: 0 publications found

Genes affected

CKS1B (HGNC:19083): (CDC28 protein kinase regulatory subunit 1B) CKS1B protein binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. The CKS1B mRNA is found to be expressed in different patterns through the cell cycle in HeLa cells, which reflects a specialized role for the encoded protein. At least two transcript variants have been identified for this gene, and it appears that only one of them encodes a protein. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.863 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-154974775-CA-C is Pathogenic according to our data. Variant chr1-154974775-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1706624.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001826.3. 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
	CKS1B	NM_001826.3	MANE Select	c.33delA	p.Lys11AsnfsTer18	frameshift	Exon 1 of 3	NP_001817.1	Q5T178
	CKS1B	NR_024163.2		n.98delA		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKS1B	ENST00000308987.6	TSL:1 MANE Select	c.33delA	p.Lys11AsnfsTer18	frameshift	Exon 1 of 3	ENSP00000311083.5	P61024
	CKS1B	ENST00000368439.5	TSL:1	c.-124delA		5_prime_UTR	Exon 1 of 3	ENSP00000357424.1	Q9BZU3
	CKS1B	ENST00000913208.1		c.33delA	p.Lys11AsnfsTer53	frameshift	Exon 1 of 4	ENSP00000583267.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Breast neoplasm (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr1-154947251;