NM_001375405.1:c.1764-9_1764-5delTATTT

Variant names:

• chr5-123383086-CAAATA-C
• rs1771771063
• NM_001375405.1:c.1764-9_1764-5delTATTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375405.1(CEP120):​c.1764-9_1764-5delTATTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000403 in 1,242,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: CEP120 NM_001375405.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46
• Publications: 0 publications found

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

CEP120 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 31

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short-rib thoracic dysplasia 13 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375405.1. 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
	CEP120	NM_001375405.1	MANE Select	c.1764-9_1764-5delTATTT		splice_region intron	N/A	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.1764-9_1764-5delTATTT		splice_region intron	N/A	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.1686-9_1686-5delTATTT		splice_region intron	N/A	NP_001159698.1	Q8N960-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	ENST00000306467.10	TSL:5 MANE Select	c.1764-9_1764-5delTATTT		splice_region intron	N/A	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*1336-9_*1336-5delTATTT		splice_region intron	N/A	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.*974-9_*974-5delTATTT		splice_region intron	N/A	ENSP00000422089.2	Q8N960-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000403 AC: 5 AN: 1242054 Hom.: 0 AF XY: 0.00000479 AC XY: 3 AN XY: 626286

African (AFR) AF: 0.0000360 AC: 1 AN: 27772

American (AMR) AF: 0.00 AC: 0 AN: 34686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23278

East Asian (EAS) AF: 0.00 AC: 0 AN: 37532

South Asian (SAS) AF: 0.00 AC: 0 AN: 74184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 0.00000428 AC: 4 AN: 934984

Other (OTH) AF: 0.00 AC: 0 AN: 52456

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

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

Other links and lift over

dbSNP: rs1771771063; hg19: chr5-122718780;