rs1808140

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001382391.1(CSPP1):c.3313T>C(p.Trp1105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,610,886 control chromosomes in the GnomAD database, including 510 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 80 hom., cov: 32)

Exomes 𝑓: 0.012 ( 430 hom. )

Consequence

CSPP1
NM_001382391.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.43

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 links:

ARFGEF1 (HGNC:15772): (ADP ribosylation factor guanine nucleotide exchange factor 1) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Aug 2011]

ARFGEF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013003945).

BP6

Variant 8-67190742-T-C is Benign according to our data. Variant chr8-67190742-T-C is described in ClinVar as [Benign]. Clinvar id is 379419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-67190742-T-C is described in Lovd as [Likely_benign]. Variant chr8-67190742-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0222 (3375/152242) while in subpopulation SAS AF= 0.0462 (223/4824). AF 95% confidence interval is 0.0413. There are 80 homozygotes in gnomad4. There are 2004 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 80 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1 link	c.3313T>C	p.Trp1105Arg	missense_variant	Exon 29 of 31	ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1 link	c.3313T>C	p.Trp1105Arg	missense_variant	Exon 29 of 31		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3372

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00536

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.0223

AC:

5559

AN:

249492

Hom.:

173

AF XY:

0.0228

AC XY:

3091

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.0363

Gnomad AMR exome

AF:

0.00959

Gnomad ASJ exome

AF:

0.00636

Gnomad EAS exome

AF:

0.0127

Gnomad SAS exome

AF:

0.0444

Gnomad FIN exome

AF:

0.0973

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.0120

AC:

17543

AN:

1458644

Hom.:

430

Cov.:

AF XY:

0.0129

AC XY:

9380

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.00993

Gnomad4 ASJ exome

AF:

0.00682

Gnomad4 EAS exome

AF:

0.0242

Gnomad4 SAS exome

AF:

0.0432

Gnomad4 FIN exome

AF:

0.0866

Gnomad4 NFE exome

AF:

0.00486

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0222

AC:

3375

AN:

152242

Hom.:

Cov.:

AF XY:

0.0269

AC XY:

2004

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0344

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.0462

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00792

Hom.:

Bravo

AF:

0.0156

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.0367

AC:

142

ESP6500EA

AF:

0.00399

AC:

ExAC

AF:

0.0216

AC:

2617

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 02, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joubert syndrome 21

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.9

DANN

Benign

0.66

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.019

Sift

Benign

0.37

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.022

B;B

Vest4

0.071

MPC

0.24

ClinPred

0.0019

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.019

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over