8-67105943-AT-TC

Variant names:

• chr8-67105943-AT-TC
• NM_001382391.1:c.1061_1062delATinsTC
• CSPP1 p.Asp354Val

Variant summary

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

The NM_001382391.1(CSPP1):​c.1061_1062delATinsTC​(p.Asp354Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. D354G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSPP1 NM_001382391.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 0 publications found

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]

CSPP1 Gene-Disease associations (from GenCC):

• Joubert syndrome 21

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with Jeune asphyxiating thoracic dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382391.1. 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
	CSPP1	NM_001382391.1	MANE Select	c.1061_1062delATinsTC	p.Asp354Val	missense	N/A	NP_001369320.1	A0A7I2V5W3
	CSPP1	NM_001364869.1		c.1169_1170delATinsTC	p.Asp390Val	missense	N/A	NP_001351798.1	A0A7I2PHE7
	CSPP1	NM_024790.7		c.1088_1089delATinsTC	p.Asp363Val	missense	N/A	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000678616.1	MANE Select	c.1061_1062delATinsTC	p.Asp354Val	missense	N/A	ENSP00000504733.1	A0A7I2V5W3
	CSPP1	ENST00000262210.11	TSL:1	c.1169_1170delATinsTC	p.Asp390Val	missense	N/A	ENSP00000262210.6	A0A7I2PHE7
	CSPP1	ENST00000519668.1	TSL:1	c.206_207delATinsTC	p.Asp69Val	missense	N/A	ENSP00000430092.1	Q1MSJ5-2

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		0.99

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: chr8-68018178;