rs76567936
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1
The NM_001382391.1(CSPP1):āc.3138A>Gā(p.Lys1046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,612,298 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.015 ( 62 hom., cov: 32)
Exomes š: 0.0014 ( 43 hom. )
Consequence
CSPP1
NM_001382391.1 synonymous
NM_001382391.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.73
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 8-67177708-A-G is Benign according to our data. Variant chr8-67177708-A-G is described in ClinVar as [Benign]. Clinvar id is 379767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSPP1 | NM_001382391.1 | c.3138A>G | p.Lys1046= | synonymous_variant | 27/31 | ENST00000678616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSPP1 | ENST00000678616.1 | c.3138A>G | p.Lys1046= | synonymous_variant | 27/31 | NM_001382391.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0151 AC: 2298AN: 152218Hom.: 61 Cov.: 32
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GnomAD3 exomes AF: 0.00363 AC: 904AN: 249370Hom.: 21 AF XY: 0.00280 AC XY: 379AN XY: 135294
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GnomAD4 exome AF: 0.00141 AC: 2065AN: 1459962Hom.: 43 Cov.: 28 AF XY: 0.00123 AC XY: 894AN XY: 726364
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GnomAD4 genome ? AF: 0.0151 AC: 2306AN: 152336Hom.: 62 Cov.: 32 AF XY: 0.0140 AC XY: 1046AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2016 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at