Genetic Variant CSPP1:c.2128+35_2128+36dupTT (chr8-67149947-C-CTT) – 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+35_2128+36dupTT 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 0.00055 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00067 ( 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:

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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+35_2128+36dupTT		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+35_2128+36dupTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.000548

AC:

AN:

89468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000173

Gnomad AMI

AF:

0.00167

Gnomad AMR

AF:

0.000872

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000749

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000667

AC:

699

AN:

1047700

Hom.:

Cov.:

AF XY:

0.000696

AC XY:

360

AN XY:

516912

show subpopulations

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

African (AFR)

AF:

0.000453

AC:

AN:

22080

American (AMR)

AF:

0.00111

AC:

AN:

17984

Ashkenazi Jewish (ASJ)

AF:

0.000130

AC:

AN:

15338

East Asian (EAS)

AF:

0.000787

AC:

AN:

29208

South Asian (SAS)

AF:

0.00139

AC:

AN:

43082

European-Finnish (FIN)

AF:

0.000442

AC:

AN:

36218

Middle Eastern (MID)

AF:

0.000617

AC:

AN:

3240

European-Non Finnish (NFE)

AF:

0.000650

AC:

544

AN:

837558

Other (OTH)

AF:

0.000512

AC:

AN:

42992

⚠️ 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: 0.262

Heterozygous variant carriers

162

242

323

404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000548

AC:

AN:

89440

Hom.:

Cov.:

AF XY:

0.000705

AC XY:

AN XY:

41162

show subpopulations

African (AFR)

AF:

0.000173

AC:

AN:

23114

American (AMR)

AF:

0.000872

AC:

AN:

8026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2460

East Asian (EAS)

AF:

0.000968

AC:

AN:

3100

South Asian (SAS)

AF:

0.00

AC:

AN:

2518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.000749

AC:

AN:

45370

Other (OTH)

AF:

0.00

AC:

AN:

1170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.00

Hom.:

1063

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism

(source)

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