rs587777138

Variant names:

• chr8-67158540-C-A
• rs587777138
• NM_001382391.1:c.2335C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-67158540-C-A
• chr8-67158540-C-G
• chr8-67158540-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001364869.1(CSPP1):​c.2401C>A​(p.Arg801Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSPP1 NM_001364869.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593
• Publications: 0 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.593 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364869.1. 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.2335C>A	p.Arg779Arg	synonymous	Exon 20 of 31	NP_001369320.1
	CSPP1	NM_001364869.1		c.2401C>A	p.Arg801Arg	synonymous	Exon 19 of 30	NP_001351798.1
	CSPP1	NM_024790.7		c.2320C>A	p.Arg774Arg	synonymous	Exon 18 of 29	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000678616.1	MANE Select	c.2335C>A	p.Arg779Arg	synonymous	Exon 20 of 31	ENSP00000504733.1
	CSPP1	ENST00000262210.11	TSL:1	c.2401C>A	p.Arg801Arg	synonymous	Exon 19 of 30	ENSP00000262210.6
	CSPP1	ENST00000519668.1	TSL:1	c.1285C>A	p.Arg429Arg	synonymous	Exon 15 of 26	ENSP00000430092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458632 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725622

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.0000224 AC: 1 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109914

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.3
DANN	Benign	0.59
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs587777138; hg19: chr8-68070775;