rs1554614893

chr8-67172403-CATTTATCTATAGGAAAAAGGAAAGGAATCCCATGGATATATTTGATATGGCTAGACATCGGTTGCAAGCTCCTGTCAGAAGACAGTCCCCTAAGGGCTTAGACGCTGCCACTTTTCAGAATGTTCATGATTTTAATGAGCTGAAAGATAGAGGTGAGTAG-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001382391.1(CSPP1):c.2829-9_2968+11del variant causes a splice acceptor, splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSPP1 NM_001382391.1 splice_acceptor, splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.946

Genes affected

CSPP1 (HGNC:26193): (centrosome and spindle pole associated protein 1) This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-67172403-CATTTATCTATAGGAAAAAGGAAAGGAATCCCATGGATATATTTGATATGGCTAGACATCGGTTGCAAGCTCCTGTCAGAAGACAGTCCCCTAAGGGCTTAGACGCTGCCACTTTTCAGAATGTTCATGATTTTAATGAGCTGAAAGATAGAGGTGAGTAG-C is Pathogenic according to our data. Variant chr8-67172403-CATTTATCTATAGGAAAAAGGAAAGGAATCCCATGGATATATTTGATATGGCTAGACATCGGTTGCAAGCTCCTGTCAGAAGACAGTCCCCTAAGGGCTTAGACGCTGCCACTTTTCAGAATGTTCATGATTTTAATGAGCTGAAAGATAGAGGTGAGTAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 434846.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPP1	NM_001382391.1	c.2829-9_2968+11del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	25/31	ENST00000678616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPP1	ENST00000678616.1	c.2829-9_2968+11del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	25/31		NM_001382391.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 21 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 04, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554614893; hg19: chr8-68084638;