1-154974775-CA-C

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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

Verdict is Likely_pathogenic. Variant got 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 0 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 id is 1706624.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKS1B	NM_001826.3	c.33delA	p.Lys11AsnfsTer18	frameshift_variant	Exon 1 of 3	ENST00000308987.6	NP_001817.1
CKS1B	NR_024163.2	n.98delA		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKS1B	ENST00000308987.6	c.33delA	p.Lys11AsnfsTer18	frameshift_variant	Exon 1 of 3	1	NM_001826.3	ENSP00000311083.5
CKS1B	ENST00000368439.5	c.-124delA		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000357424.1
CKS1B	ENST00000368436.1	c.33delA	p.Lys11AsnfsTer18	frameshift_variant	Exon 1 of 2	2		ENSP00000357421.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Breast neoplasm Pathogenic:1

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Genomic Center, National Cancer Institute

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154947251;