8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr8-67149947-C-CTTTTTTTTTT
• rs11296619
• NM_001382391.1:c.2128+27_2128+36dupTTTTTTTTTT

Variant summary

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

The NM_001364869.1(CSPP1):​c.2194+27_2194+36dupTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CSPP1 NM_001364869.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• 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, Labcorp Genetics (formerly Invitae), G2P
• 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_001364869.1. 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.2128+27_2128+36dupTTTTTTTTTT		intron	N/A	NP_001369320.1
	CSPP1	NM_001364869.1		c.2194+27_2194+36dupTTTTTTTTTT		intron	N/A	NP_001351798.1
	CSPP1	NM_024790.7		c.2113+27_2113+36dupTTTTTTTTTT		intron	N/A	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000678616.1	MANE Select	c.2128+12_2128+13insTTTTTTTTTT		intron	N/A	ENSP00000504733.1
	CSPP1	ENST00000262210.11	TSL:1	c.2194+12_2194+13insTTTTTTTTTT		intron	N/A	ENSP00000262210.6
	CSPP1	ENST00000519668.1	TSL:1	c.1079-4077_1079-4076insTTTTTTTTTT		intron	N/A	ENSP00000430092.1

Frequencies

GnomAD3 genomes AF: 0.0000671 AC: 6 AN: 89446 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000866

Gnomad AMI AF: 0.00167

Gnomad AMR AF: 0.000125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 13 AN: 1049684 Hom.: 0 Cov.: 0 AF XY: 0.0000174 AC XY: 9 AN XY: 517924

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22100

American (AMR) AF: 0.0000556 AC: 1 AN: 17998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15356

East Asian (EAS) AF: 0.0000342 AC: 1 AN: 29252

South Asian (SAS) AF: 0.0000463 AC: 2 AN: 43172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3248

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 839214

Other (OTH) AF: 0.00 AC: 0 AN: 43090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000671 AC: 6 AN: 89446 Hom.: 0 Cov.: 0 AF XY: 0.0000486 AC XY: 2 AN XY: 41150

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000866 AC: 2 AN: 23084

American (AMR) AF: 0.000125 AC: 1 AN: 8028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2460

East Asian (EAS) AF: 0.00 AC: 0 AN: 3114

South Asian (SAS) AF: 0.00 AC: 0 AN: 2532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.0000441 AC: 2 AN: 45366

Other (OTH) AF: 0.00 AC: 0 AN: 1166

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000651256), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs11296619; hg19: chr8-68062182;