Genetic Variant CSPP1:c.2128+34_2128+36dupTTT (chr8-67149947-C-CTTT) – 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+34_2128+36dupTTT 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 0.000034 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00015 ( 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+34_2128+36dupTTT		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+34_2128+36dupTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.0000335

AC:

AN:

89466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000433

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000340

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000220

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000148

AC:

155

AN:

1049160

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

517656

show subpopulations

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

African (AFR)

AF:

0.000136

AC:

AN:

22092

American (AMR)

AF:

0.000111

AC:

AN:

17996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15344

East Asian (EAS)

AF:

0.000239

AC:

AN:

29234

South Asian (SAS)

AF:

0.000394

AC:

AN:

43154

European-Finnish (FIN)

AF:

0.0000276

AC:

AN:

36250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3246

European-Non Finnish (NFE)

AF:

0.000142

AC:

119

AN:

838778

Other (OTH)

AF:

0.000139

AC:

AN:

43066

⚠️ 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: 0.266

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:

0.0000335

AC:

AN:

89466

Hom.:

Cov.:

AF XY:

0.0000243

AC XY:

AN XY:

41164

show subpopulations

African (AFR)

AF:

0.0000433

AC:

AN:

23090

American (AMR)

AF:

0.00

AC:

AN:

8032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2458

East Asian (EAS)

AF:

0.00

AC:

AN:

3114

South Asian (SAS)

AF:

0.00

AC:

AN:

2532

European-Finnish (FIN)

AF:

0.000340

AC:

AN:

2940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.0000220

AC:

AN:

45376

Other (OTH)

AF:

0.00

AC:

AN:

1166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over