Genetic Variant NM_001382391.1:c.2128+36dupT (chr8-67149947-C-CT) – 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+36dupT 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 0.00049 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0057 ( 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+36dupT		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+36dupT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.000492

AC:

AN:

89384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000520

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000407

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00119

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000508

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00324

AC:

217

AN:

66916

AF XY:

0.00298

show subpopulations

Gnomad AFR exome

AF:

0.00439

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00174

Gnomad EAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00569

AC:

5936

AN:

1042846

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

2900

AN XY:

514582

show subpopulations

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

African (AFR)

AF:

0.00473

AC:

104

AN:

21978

American (AMR)

AF:

0.00429

AC:

AN:

17954

Ashkenazi Jewish (ASJ)

AF:

0.00478

AC:

AN:

15280

East Asian (EAS)

AF:

0.00640

AC:

186

AN:

29078

South Asian (SAS)

AF:

0.00757

AC:

325

AN:

42936

European-Finnish (FIN)

AF:

0.00376

AC:

136

AN:

36136

Middle Eastern (MID)

AF:

0.00653

AC:

AN:

3218

European-Non Finnish (NFE)

AF:

0.00569

AC:

4745

AN:

833472

Other (OTH)

AF:

0.00629

AC:

269

AN:

42794

⚠️ 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: 0.265

Heterozygous variant carriers

639

1278

1917

2556

3195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

204

408

612

816

1020

<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:

0.000492

AC:

AN:

89354

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

AN XY:

41118

show subpopulations

African (AFR)

AF:

0.000520

AC:

AN:

23092

American (AMR)

AF:

0.00

AC:

AN:

8026

Ashkenazi Jewish (ASJ)

AF:

0.000407

AC:

AN:

2460

East Asian (EAS)

AF:

0.000968

AC:

AN:

3100

South Asian (SAS)

AF:

0.00119

AC:

AN:

2516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2938

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.000508

AC:

AN:

45312

Other (OTH)

AF:

0.00

AC:

AN:

1170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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