Variant 8-67149929-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001382391.1(CSPP1):c.2122A>G(p.Ser708Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000418 in 1,557,668 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 8 hom. )

Consequence

CSPP1
NM_001382391.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.87

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:

CSPP1 (HGNC:):

CSPP1 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=0.0044882894).

BP6

Variant 8-67149929-A-G is Benign according to our data. Variant chr8-67149929-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 541697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000319 (48/150602) while in subpopulation SAS AF= 0.00987 (47/4764). AF 95% confidence interval is 0.00762. There are 2 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPP1	NM_001382391.1 linkuse as main transcript	c.2122A>G	p.Ser708Gly	missense_variant	18/31	ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1 linkuse as main transcript	c.2122A>G	p.Ser708Gly	missense_variant	18/31		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.000326

AC:

AN:

150494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00101

AC:

196

AN:

193808

Hom.:

AF XY:

0.00119

AC XY:

127

AN XY:

107024

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00857

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000954

GnomAD4 exome

AF:

0.000429

AC:

603

AN:

1407066

Hom.:

Cov.:

AF XY:

0.000595

AC XY:

416

AN XY:

699284

show subpopulations

Gnomad4 AFR exome

AF:

0.0000332

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00732

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.000727

GnomAD4 genome

AF:

0.000319

AC:

AN:

150602

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

AN XY:

73496

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00987

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.00115

AC:

139

Asia WGS

AF:

0.00202

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

CSPP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.12

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.50

REVEL

Benign

0.027

Sift

Benign

0.50

Sift4G

Benign

0.37

Polyphen

0.0010

Vest4

0.34

MVP

0.29

MPC

0.11

ClinPred

0.080

GERP RS

6.0

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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