rs370003497

Variant names:

• chr8-67074303-C-T
• rs370003497
• NM_001382391.1:c.51C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001382391.1(CSPP1):​c.51C>T​(p.Ala17Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,608,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: CSPP1 NM_001382391.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.103
• Publications: 1 publications found

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]

COPS5 (HGNC:2240): (COP9 signalosome subunit 5) The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be an coactivator that increases the specificity of JUN/AP1 transcription factors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 8-67074303-C-T is Benign according to our data. Variant chr8-67074303-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 386180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.103 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382391.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	NM_001382391.1	MANE Select	c.51C>T	p.Ala17Ala	synonymous	Exon 2 of 31	NP_001369320.1	A0A7I2V5W3
	CSPP1	NM_001364869.1		c.159C>T	p.Ala53Ala	synonymous	Exon 2 of 30	NP_001351798.1	A0A7I2PHE7
	CSPP1	NM_024790.7		c.159C>T	p.Ala53Ala	synonymous	Exon 2 of 29	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000678616.1	MANE Select	c.51C>T	p.Ala17Ala	synonymous	Exon 2 of 31	ENSP00000504733.1	A0A7I2V5W3
	CSPP1	ENST00000262210.11	TSL:1	c.159C>T	p.Ala53Ala	synonymous	Exon 2 of 30	ENSP00000262210.6	A0A7I2PHE7
	CSPP1	ENST00000676605.1		c.282C>T	p.Ala94Ala	synonymous	Exon 3 of 30	ENSP00000503605.1	A0A7I2V3V5

Frequencies

GnomAD3 genomes AF: 0.000382 AC: 58 AN: 151768 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000284 AC: 70 AN: 246290 AF XY: 0.000239

Gnomad AFR exome AF: 0.000261

Gnomad AMR exome AF: 0.0000888

Gnomad ASJ exome AF: 0.000600

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000491

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000430 AC: 626 AN: 1456654 Hom.: 0 Cov.: 29 AF XY: 0.000436 AC XY: 316 AN XY: 724638

African (AFR) AF: 0.0000902 AC: 3 AN: 33244

American (AMR) AF: 0.000158 AC: 7 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 15 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.000520 AC: 577 AN: 1109236

Other (OTH) AF: 0.000366 AC: 22 AN: 60106

GnomAD4 genome AF: 0.000382 AC: 58 AN: 151768 Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74078

African (AFR) AF: 0.0000969 AC: 4 AN: 41276

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000442 Hom.: 0

Bravo AF: 0.000434

EpiCase AF: 0.000385

EpiControl AF: 0.000420

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Joubert syndrome 21 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.2
DANN	Benign	0.55
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs370003497; hg19: chr8-67986538;