Genetic Variant CSPP1:c.2128+29_2128+36dupTTTTTTTT (chr8-67149947-C-CTTTTTTTT) – 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+29_2128+36dupTTTTTTTT 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 0.00058 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000026 ( 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+29_2128+36dupTTTTTTTT		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+29_2128+36dupTTTTTTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.000583

AC:

AN:

89180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000608

Gnomad AMI

AF:

0.00168

Gnomad AMR

AF:

0.000874

Gnomad ASJ

AF:

0.000817

Gnomad EAS

AF:

0.000643

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000680

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000509

Gnomad OTH

AF:

0.000862

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1049668

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

517914

show subpopulations

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

African (AFR)

AF:

0.0000452

AC:

AN:

22100

American (AMR)

AF:

0.0000556

AC:

AN:

17998

Ashkenazi Jewish (ASJ)

AF:

0.000130

AC:

AN:

15356

East Asian (EAS)

AF:

0.0000342

AC:

AN:

29250

South Asian (SAS)

AF:

0.000162

AC:

AN:

43168

European-Finnish (FIN)

AF:

0.0000276

AC:

AN:

36256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

839202

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: 0.301

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:

0.000583

AC:

AN:

89152

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

AN XY:

41054

show subpopulations

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

African (AFR)

AF:

0.000607

AC:

AN:

23052

American (AMR)

AF:

0.000874

AC:

AN:

8008

Ashkenazi Jewish (ASJ)

AF:

0.000817

AC:

AN:

2448

East Asian (EAS)

AF:

0.000646

AC:

AN:

3096

South Asian (SAS)

AF:

0.00

AC:

AN:

2514

European-Finnish (FIN)

AF:

0.000680

AC:

AN:

2940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.000509

AC:

AN:

45194

Other (OTH)

AF:

0.000859

AC:

AN:

1164

⚠️ 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: 0.254

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:

0.00424

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

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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