Genetic Variant CSPP1:c.2128+28_2128+36dupTTTTTTTTT (chr8-67149947-C-CTTTTTTTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001382391.1(CSPP1):c.2128+28_2128+36dupTTTTTTTTT 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 0.00029 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CSPP1
NM_001382391.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

Publications

0 publications found

Variant links:

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

CSPP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1 link	c.2128+28_2128+36dupTTTTTTTTT		intron_variant	Intron 18 of 30	ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1 link	c.2128+28_2128+36dupTTTTTTTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.000291

AC:

AN:

89336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000174

Gnomad AMI

AF:

0.00334

Gnomad AMR

AF:

0.000249

Gnomad ASJ

AF:

0.000407

Gnomad EAS

AF:

0.000321

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000858

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1049682

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

517920

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

22100

American (AMR)

AF:

0.00

AC:

AN:

17998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15356

East Asian (EAS)

AF:

0.0000684

AC:

AN:

29252

South Asian (SAS)

AF:

0.000116

AC:

AN:

43174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.00000596

AC:

AN:

839210

Other (OTH)

AF:

0.00

AC:

AN:

43090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.283

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000291

AC:

AN:

89308

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

41112

show subpopulations

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

African (AFR)

AF:

0.000173

AC:

AN:

23076

American (AMR)

AF:

0.000249

AC:

AN:

8020

Ashkenazi Jewish (ASJ)

AF:

0.000407

AC:

AN:

2460

East Asian (EAS)

AF:

0.000323

AC:

AN:

3098

South Asian (SAS)

AF:

0.00

AC:

AN:

2516

European-Finnish (FIN)

AF:

0.000340

AC:

AN:

2940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

45288

Other (OTH)

AF:

0.000855

AC:

AN:

1170

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00290

Hom.:

1063

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.3

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over