rs6595440

Variant names:

• chr5-123383042-G-A
• rs6595440
• NM_001375405.1:c.1804C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-123383042-G-A
• chr5-123383042-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001375405.1(CEP120):​c.1804C>T​(p.Leu602Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,417,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CEP120 NM_001375405.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.83
• Publications: 41 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 5-123383042-G-A is Benign according to our data. Variant chr5-123383042-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3015443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.84 with no splicing effect.

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.1804C>T	p.Leu602Leu	synonymous	Exon 12 of 20	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.1804C>T	p.Leu602Leu	synonymous	Exon 13 of 21	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.1726C>T	p.Leu576Leu	synonymous	Exon 12 of 20	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.1804C>T	p.Leu602Leu	synonymous	Exon 12 of 20	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*1376C>T		non_coding_transcript_exon	Exon 15 of 23	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.*1014C>T		non_coding_transcript_exon	Exon 12 of 21	ENSP00000422089.2	Q8N960-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000155 AC: 22 AN: 1417862 Hom.: 0 Cov.: 26 AF XY: 0.0000141 AC XY: 10 AN XY: 707552

African (AFR) AF: 0.00 AC: 0 AN: 32644

American (AMR) AF: 0.00 AC: 0 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 84338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.0000195 AC: 21 AN: 1074204

Other (OTH) AF: 0.0000170 AC: 1 AN: 58808

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3299

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Short-rib thoracic dysplasia 13 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		2.8

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: rs6595440; hg19: chr5-122718736;